Chronic lower extremity wounds present a medical challenge because

Transcription

1 ORIGINAL RESEARCH Prediction of Wound Healing Outcome Using Skin Perfusion Pressure and Transcutaneous Oximetry: A Single-Center Experience in 100 Patients Takkin Lo, MD, MPH, CWS; Richard Sample, BSPH; Patrick Moore, MBA; Philip Gold, MD WOUNDS 2009;21(11): From the Wound Treatment Center & Hyperbaric Medicine Service, Loma Linda University Medical Center, Loma Linda, California Address correspondence to: Takkin Lo, MD, MPH, CWS Wound Treatment Center & Hyperbaric Medicine Service Loma Linda University Medical Center Anderson St. Loma Linda, CA Phone: TLo@llu.edu Abstract: Chronic lower extremity wounds are challenging and typically occur in patients with complicating conditions such as diabetes and peripheral vascular disease. Noninvasive modalities developed to assess wound healing potential, such as transcutaneous oximetry (TcPO2), present problems including lengthy test time, variable results, and anatomical limitations. Skin perfusion pressure (SPP) testing appears to be a timely, objective, and reliable alternative. This prospective, single center, comparative study evaluated TcPO2 and SPP test results in 100 patients with chronic extremity wounds to determine their accuracy and usefulness in predicting wound healing potential. Concomitant baseline SPP and TcPO2 were measured and used as predictors of successful wound healing. A threshold of < 30 mmhg was selected as the cutoff below which the test was considered significantly abnormal and indicative of a wound that was unlikely to heal. Follow-up evaluations were conducted for 12 months or until healing, whichever occurred first. The study was evenly balanced for gender distribution and the mean age of the population was 63.4 years (range 19 94). Wounds were secondary to underlying diabetic, arterial, or venous conditions. SPP alone successfully predicted wound outcome in 87% of the cohort compared to TcPO2 at a rate of 64% (P < ). Furthermore, skin perfusion pressure was more sensitive in its ability to predict wound healing relative to TcPO2 (90% versus 66%; P < ). SPP with values 30 mmhg is a useful positive independent predictor of wound healing potential. The continued use and investigation of SPP as a reliable and objective measurement tool in wound assessment protocols and other microperfusion assessments are recommended. 310 WOUNDS Chronic lower extremity wounds present a medical challenge because they fail to respond to established medical and surgical management in a timely manner. Often, these patients present with multiple local and systemic factors that may impact wound healing including diabetes mellitus, chronic venous insufficiency, hypertension, and peripheral vascular dis-

2 ease. Beyond the 20.8 million Americans with known diabetes, 1 another 6.2 million remain undiagnosed and are unaware they have the disease. 2 A frequently seen complication of diabetes mellitus is lower extremity ulceration (LEU). Patients with diabetes admitted to a hospital with a LEU are hospitalized longer on average than those who do not have ulcers,3,4 and while the majority of foot ulcers are managed in an outpatient setting, hospitalization accounts for approximately three quarters of the total expenditures on medical care related to diabetic foot ulcers. 5 Impacting this population even further is that half of all lower extremity amputations occur in diabetic patients. 3,4 Those undergoing a lower extremity amputation experience a diminished quality of life in addition to increased healthcare costs the latter was confirmed by a health maintenance organization cost analysis utilizing data from The analysis revealed that the cost attributed to a lower extremity ulcer for the 2 years following diagnosis was $27, Diabetic amputees frequently have numerous comorbidities, are more likely to have their contralateral limb amputated, and have a high 5-year mortality rate. 6,7 Given the significant population of patients with lower extremity wounds and the limitations of existing noninvasive diagnostic tests to predict wound healing success, identification of the most effective method to predict which wounds will heal and/or the determination of the optimal amputation level for those that will not, is an important health and economic priority. The authors believe that TCOM can be used effectively for these purposes. However, considering the limitations associated with this technology, the authors experience supports its use in conjunction with other noninvasive modalities. One such modality, skin perfusion pressure (SPP), merits serious consideration as an assessment of the functional ability of the capillaries to support wound healing. Skin perfusion pressure is a measurement of the pressure at which perfusion first returns to the cutaneous microcirculation following a controlled release of occlusion. It combines the use of a laser Doppler and a pressure cuff. Literature suggests that SPP measurements are not affected by edema, anemia, callus, or wound location. 8,9 Similar to TCOM, studies have shown that chronic extremity wounds with an SPP < 30 mmhg have a low probability of healing. 9,10 Although measuring different parameters (TcPO2 assesses tissue oxygenation; SPP assesses capillary perfusion), SPP theoretically could be considered a functional test of capillary bed vitality, and as such, should correlate with TcPO2 (ie, values 30 mmhg provide confirmation of successful delivery of oxygen into cutaneous capillary beds). Therefore, these different technologies were evaluated for their ability to accurately predict healing outcomes in patients who presented with chronic lower extremity wound. The primary objective of this clinical research was to determine the accuracy and usefulness of SPP measurements when compared to TcPO2 measurements for wound assessment. Accordingly, after confirmed wound healing, baseline TcPO2 data were compared to baseline SPP data to determine which measurement was more predictive of wound healing. Measurements were obtained for research purposes and were not used for clinical decision-making. Materials and Methods This prospective, comparative study was conducted over a 5-year period from December 1998 to October 2003 at the Wound Treatment Center & Hyperbaric Medicine Service (Loma Linda University Medical Center).Approval was obtained from the governing IRB. Patients were enrolled throughout the summer and fall seasons from due to research staff availability. All patients were treated equally with the wound center s standard comprehensive wound care protocol. Concurrent SPP and TcPO2 measurements were obtained for 100 patients with chronic lower extremity wounds. To be considered for the study, a wound must have been present for a minimum of 8 weeks; however, it should be noted that many of the patients presenting to the clinic for treatment displayed wounds that had been present for many years and in some cases, even decades. For study purposes, a chronic wound was defined as a full- or partial-thickness wound that failed to achieve anatomic and functional integrity within 8 weeks. All patients age 18 years who presented with a chronic lower extremity wound were invited to participate. Study participants provided written informed consent. SPP and TcPO2 values of 30 mmhg were used to predict a positive outcome (healing) Although patients were evaluated more frequently, data capture was conducted at baseline, 6 months, and 12 months. Test descriptors. Patients were placed in a standard treatment room where the temperature was regulated at 72 F. Measurements were performed concurrently with the SPP testing being conducted first. Patients were tested while breathing room air. Ideal positioning consisted of a supine or semi-fowler s position; the majority of Vol. 21, No. 11 November

3 patients were positioned in a supine fashion. The selected measurement sites were as close to the wound as was reasonable, but not directly on the wound. Patient preparation for each testing method occurred simultaneously as described below. TcPO2 preparation. TcPO2 measurements were performed utilizing the Radiometer TCM3 (Radiometer, Copenhagen, Denmark). Local hair was removed and the area was cleansed with an alcohol wipe followed by subsequent applications and removal of adhesive tape to effectively eliminate the stratum corneum. This procedure ensured optimal TcPO2 electrode contact for skin oxygen diffusion. Following adequate site preparation, the TcPO2 adhesive ring was positioned appropriately. Sufficient contact solution was applied to the reservoir after ensuring complete coverage of the exposed skin surface within the adhesive ring. The electrode was then connected to the adhesive ring and supported to avoid external tension at the electrode site. Electrode temperature was measured at 44.5 C. Testing sites avoided bony prominences, superficial blood vessels, calluses, flaky skin, and edema. SPP preparation. Skin perfusion pressure measurement was made using the PV 2000 Skin Perfusion Pressure System (Väsamed, Inc, Eden Prairie, MN). This unit featured a laser Doppler sensor embedded in an inflatable pressure cuff. The cuff was applied appropriately on the lower extremity with the laser sensor being positioned as close to the proximal wound edge as reasonable. Testing sites avoided bony prominences, veins, arteries, and tendons. Testing procedures. While the TcPO2 electrode was allowed to complete the necessary 15-minute warm up time, the skin perfusion pressure measurement was initiated by inflation of the cuff. As the pressure increased, the microvasculature was compressed, resulting in a decrease and eventual temporary cessation of capillary blood flow beneath the cuff. Following attainment of the temporary occlusion, the cuff pressure was slowly deflated. The pressure at which perfusion first returned to the skin microcirculation was observed and recorded. At the completion of the SPP measurement and 15 minutes after the TcPO2 electrode was placed, the TcPO2 measurement was performed and recorded. Concomitantly measured baseline SPP data were compared to baseline TcPO2 as predictors of successful wound healing. Complete wound healing was selfdefined; partial wound healing was defined as > 50% reduction in the wound size when compared to the baseline wound dimensions. Confirmation of complete wound healing was accomplished through the following hierarchical structure: physical examination, chart review, and, verbal confirmation through telephone contact when either of the previous options were unattainable. Statistical Analysis Descriptive statistics including means, standard deviations, medians, minimums, and maximums were presented for baseline characteristics. Frequencies and percentages were presented for comorbidities and wound descriptors. Fisher s exact tests were used to test for associations between the diagnostic tests and wound healing status. Sensitivity, specificity, and predictive values were used to assess the accuracy of TcPO2 and SPP in predicting wound healing status at 12 months. Sensitivity related to how well the technology predicts wound healing and specificity related to the ability of SPP or TcPO2 to correctly predict when a wound would not ultimately heal. Wounds were separated into two groups (healed and nonhealed) for analyses purposes. SAS version 9.1 was used for statistical calculations. Results Baseline demographics for the study cohort are presented in Table 1. It is important to note that in this patient pool, only 17% had 2 co-morbidity factors; the remaining 83% of the patients presented with 3 to 9 comorbidities. Furthermore, it was observed that 52% tested positive for diabetes (of which 24 were insulindependent), 36% had documented PVD, and 62% presented with hypertension, 85% (53/62) of whom were medically managed with antihypertensive medications. The rate of obesity was 33%. Other co-morbid factors included chronic venous insufficiency (42%), atherosclerotic heart disease (36%), cellulitis (33%), current or remote tobacco use (28%), osteomyelitis (21%), congestive heart failure (20%), acute or chronic renal disease (18%), anemia (14%), cerebral vascular accident with or without paraplegia/quadriplegia (9%), collagen vascular Table 1. Baseline demographics. Variable Mean (± SD) Median Range Age (years) Height (inches) Weight (pounds) Systolic BP (mmhg) Diastolic BP (mmhg) WOUNDS

4 Table 2. Wound classification descriptors. Term Wagner Grade 0 Wagner Grade 1 Wagner Grade 2 Wagner Grade 3 Wagner Grade 4 Wagner Grade 5 Superficial Partial-thickness Full-thickness Description Intact skin. Superficial ulcer without penetration to deeper layers. Deeper ulcer that reaches tendon, bone, or joint capsule. Deeper ulcer with abscess, osteomyelitis, or tendonitis extending to tendon or bone. Gangrene of some portion of the toe, toes, and/or forefoot, which may be wet or dry. Gangrene involves the whole foot or enough of the foot that no local procedures are possible. Involving but not through the epidermis. Through the epidermis; into but not through the dermis. Through the epidermis and dermis into the subcutaneous tissue, fascia, etc. Table 3. Baseline wound descriptors. n Parameter Cumulative (n = 100) Location Ankle/heel Foot (dorsal) Foot (plantar) Leg (below the knee/above ankle) Wound Classification/Grade Wagner Grade I Wagner Grade II/III Wagner Grade IV/V Full-thickness/partialthickness/superficial Not specified Total classification/graded wounds /10 1/1 32/24/8 disorder (8%), neuropathy (7%), and Charcot foot (2%). Wound descriptors captured included location, etiology, and classification; Wagner Scale for diabetic wounds, and Table 4. Affected limb and edema by extremity. Limb detail Affected limb Known lower extremity edema Severity of lower extremity edema distribution Not specified Table 5. Diagnostic test prediction. Diagnostic test SPP TcPO2 Healing prediction* Yes No Yes No Healed wound (n = 87) Right Nonhealed wound (n = 13) Left Fisher s exact P value *Healing predication based on values of 30 mmhg for each test partial- or full-thickness for other wounds (Table 2). The observed wound etiology distribution for the study population was 35% diabetic, 15% peripheral arterial disease, 49% venous insufficiency, and 1% for which the etiology was unspecified. The authors recognize that in practice, many wounds may present with a mixed etiology; however, for this study, wound etiology was categorized by the predominant underlying condition (Tables 3, 4). Analysis revealed that SPP prediction and wound-healing status had a significant relationship (P = 0.02); however, TcPO2 prediction does not have a significant association with wound healing status (P = 0.76; Table 5). SPP demonstrated a greater sensitivity to predicting healing when compared to TcPO2 (89.7% and 65.5%, respectively; Table 6). There were no differences in specificity between diagnostic tests; however, the number of unhealed wounds was small. The few patients classified as partial healing at the conclusion of the study went on to achieve wound closure, as confirmed by telephone interview. In this study, a positive predictive value of 0.91 was observed for SPP. This value was similar to the TcPO2 positive predictive value of 0.88 (Table 6). Analysis revealed that both diagnostic tests appear to have a high positive predictive value. As previously stated, 13 wounds did not heal during this evaluation. Nonhealing was Vol. 21, No. 11 November

5 Table 6. Statistical measures. Diagnostic test SPP TcPO2 Measure Sensitivity* Specificity PPV NPV Sensitivity* Specificity PPV NPV Value (%) % exact confidence interval (81, 95) (14, 68) (82, 96) (13, 65) (55, 75) (14, 68) (77, 95) (5, 30) *Sensitivity refers to the proportion of positives where the test parameter correctly identified healing (ie, test value correlated with the actual healing outcome; test predicted healing/wound healed). Specificity refers to proportion of negatives where the test parameter correctly identified nonhealing (ie, test value correlated with actual nonhealing outcome; test predicted nonhealing/wound did not heal). Positive predictive value reflects the probability that the wound will ultimately heal when test parameter is 30 mmhg and is calculated as (true positive/[true positive + false positive]). Negative predictive value reflects the probability that wound will not heal when test parameter is < 30 mmhg and calculated as (true negative/[true negative + false negative]). found to be secondary to a patient s noncompliance (includes those lost to follow-up), significant gangrene involvement, and amputation. For those patients, the negative predictive values for SPP and TcPO2 were 0.36 and 0.14, respectively. Discussion Although these data were collected some time ago, the information contained herein is important since there continues to be a paucity of literature comparing these two technologies. Consistent with the wide-ranging patient population seeking treatment within the authors clinic setting, study participants suffered from multiple comorbidities. Compared to the general population and historical observation of patients spanning the authors career, the patients in the present study were sicker when accounting for the rates of diabetes, peripheral vascular compromise, and hypertension; although, the rate of obesity noted in the cohort (33%) was comparable to the general population. It is understood that in addition to the primary diagnoses, the clinical progression of a patient s wound(s) is influenced by the presence and incidence of comorbidities. Healing is further confounded by factors such as age, wound location, and underlying etiology. For example, patients with venous disease not only have a significant rate of wound recurrence (as high as 72%) but often have lengthy wound duration (> 1 year in 50% of patients with venous disease). 14 While the wound etiology distribution in the current investigation is not balanced, each of the cited etiologies independently contributes to delayed healing. Therefore, successful wound care management protocols should be predicated upon testing that accurately and consistently predicts medical outcomes. Skin perfusion pressure is a functional measure of the capillary bed s ability to both accommodate and transport fluid while TCOM provides metabolic confirmation that oxygen is present in blood and plasma. Transcutaneous oxygen measurement has long been regarded as the best predictor of wound healing failure at levels less than 30 mmhg. 15 Studies from Karolinska Hospital demonstrate that TcPO2 measured at the dorsum of the foot is a better predictor of healing of chronic diabetic foot ulcers than toe blood pressure, 16,17 and it is commonly accepted that toe-brachial pressures are a more sensitive measurement tool than ankle-brachial pressures in patients presenting with arterial calcification the hallux is less affected than the noncompressible calcified ankle arteries in toe-brachial pressure measurements. A TCOM study conducted by Fife et al 18 provides evidence that an increase of in-chamber TcPO2 values conferred a positive predictive outcome for wound healing. However, this same study also demonstrated that room air TcPO2 data were not useful in predicting wound healing during hyperbaric oxygen therapy 18,19 suggesting that TcPO2 may have a more important role as a complimentary, rather than a primary, parameter in wound healing assessment in many instances. TcPO2 also has inherent limitations as mentioned above. Skin perfusion pressure is a measure of distal arterial perfusion and may be representative of both arterial and collateral flow. It uses an occlusive cuff and laser Doppler to achieve and evaluate a state of reactive hyperemia. Researchers have advocated its use to assess wound healing potential, diagnose chronic limb ischemia, and assist in amputation planning Contemporary publications support these conclusions and suggest expanded applications, such as complementing revascularization therapy Advancements in endovascular devices have increased the clinician s ability to impact outcomes. Skin perfusion pressure evaluated 314 WOUNDS

6 early in the assessment process can provide accurate information as well as aid in initiating the appropriate treatments such as debridement, revascularization, or amputation much sooner. Furthermore, timely access to objective point-of-care data may help avoid initiation of costly wound care that has low potential for success. Until recently, SPP was not widely available and therefore, was not systematically evaluated in the context of a wound care clinic s unique needs. Technological improvements in software development, use of microprocessors, and full automation of the testing procedure device used in this investigation, have moved SPP measurement to the forefront providing faster, more reproducible, and reliable diagnostic clinical information. Multiple pressure cuff sizes accommodate dimensional anatomical variances allowing for testing of all extremities, including the digits. For significantly larger limbs (eg, calf of a morbidly obese patient), a cuff extender is afforded that is easily applied. To the authors knowledge, cuff size does not affect SPP values obtained, provided that the proper cuff size is utilized. Although more versatile than TCOM, SPP is not without limitations. The cuff inflation required to occlude capillary flow may occasionally be too painful for some patients. The sensor cannot be placed over bone, large vessels, or on nonblanching tissue. Understanding angiosome physiology and alternative sensor placement that complements the angiosome principles offer ways to overcome these anatomic considerations. Additionally, patients with a marked tremor (eg, Parkinson s disease) may create noise artifacts in the laser Doppler reading making SPP determination difficult or even impossible. There are simple ways to reduce the tremor effect, such as the placement of mechanical supports (rolled towels/pillows, etc.) effectively around the limb or direct hand-held support to the plantar aspect of the foot. Newer advances in SPP technology purportedly reduce the motion artifact. Overall, SPP is technically easy to use and is time efficient. Conclusion The costs of chronic lower extremity wounds in terms of financial impact and quality of life are well documented throughout the literature. The combined effect of these costs on the healthcare system make it incumbent upon healthcare providers to offer the best possible prediction of wound healing success and ultimately, provide objective input to guide the spectrum of treatments. In the present study, SPP was found to be a better predictor of wound healing outcomes than TcPO2. SPP was easy to use and demonstrated a high degree of accuracy. While it appears that both SPP and TcPO2 measurements have complimentary applications in various diagnostic and therapeutic protocols, SPP is emerging as a reliable and objective measurement tool in wound evaluation and other distal arterial assessments. References 1. Centers for Disease Control and Prevention. National Diabetes Fact Sheet: General Information and National Estimates on Diabetes in the United States, Atlanta, GA: US Department of Health and Human Services; Centers for Disease Control and Prevention. Diabetes at a Glance: Disabling Disease to Double by Atlanta, GA: US Department of Health and Human Services; April National Diabetes Data Group. Diabetes in America. Vol. 2. Bethesda, MD: National Institutes of Health; NIH publication Reiber GE. The epidemiology of diabetic foot problems. Diabet Med. 1996;13(Suppl 1):S6 S Ramsey SD, Newton K, Blough D, et al. Incidence, outcomes, and cost of foot ulcers in patients with diabetes. Diabetes Care. 1999;22(3): Brod M. Quality of life issues in patients with diabetes and lower extremity ulcers: patients and care givers. Qual Life Res. 1998;7(4): Ashry HR, Lavery LA, Armstrong DG, Lavery DC, van Houtum WH. Cost of diabetes related amputations in minorities. J Foot Ankle Surg. 1998;37(3): Holstein P, Lassen NA. Healing of ulcers on the feet correlated with distal blood pressure measurements in occlusive arterial disease. Acta Orthop Scand. 1980;51(6): Adera HM, James K, Castronuovo JJ Jr, Byrne M, Deshmukh R, Lohr J. Prediction of amputation wound healing with skin perfusion pressure. J Vasc Surg. 1995;21(5): Castronuovo JJ Jr, 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): Castronuovo JJ Jr. Diagnosis of critical limb ischemia with skin perfusion pressure measurements. J Vasc Technol. 1997;21(3): Castronuovo JJ Jr. The role of skin perfusion pressure and transcutaneous partial pressure oxygen measurements in chronic critical limb ischemia. In: Mansour MA, Vol. 21, No. 11 November

7 Labropoulos N, eds. Vascular Diagnosis. New York, NY: WB Saunders; 2005: Shefield PJ. Tissue Oxygen Measurements. In: Davis J, Hunt T, eds. Problem Wounds: The Role of Oxygen. New York, NY: Elsevier; 1988: Callam MJ, Harper DR, Dale JJ, Ruckley CV. Chronic ulcer of the leg: clinical history. Br Med J. 1987;294(6584): Frykberg RG, Zgonis T, Armstrong DG, et al. Diabetic foot disorders. A clinical practice guideline. J Foot Ankle Surg. 2006;45(5 Suppl): S1 S Kalani M, Brismar K, Fagrell B, Ostergren J, Jörneskog G. Transcutaneous oxygen tension and toe blood pressure as predictors for outcome of diabetic foot ulcers. Diabetes Care. 1999;22(1): Jörneskog G, Brismar K, Fagrell B. Skin capillary circulation is more impaired in the toes of diabetic than non-diabetic patients with peripheral vascular disease. Diabet Med. 1995;12(1): Fife CE, Buyukcakir C, Otto GH, et al. The predictive value of transcutaneous oxygen tension measurement in diabetic lower extremity ulcers treated with hyperbaric oxygen therapy: a retrospective analysis of 1,144 patients. Wound Repair Regen. 2002;10(4): Centers for Medicare and Medicaid Services. Decision Memorandum: Hyperbaric Oxygen Therapy (HBO) for Hypoxic Wounds and Diabetic Wounds of the Lower Extremities. August 30, Publication CAG-00060N. 20. Tsai FW, Tulsyan N, Jones DN, Abdel-Al N, Castronuovo JJ Jr, Carter SA. Skin perfusion pressure of the foot is a good substitute for toe pressure in the assessment of limb ischemia. J Vasc Surg. 2000;32(1): Okamoto K, Oka M, Maesato K, et al. Peripheral arterial occlusive disease is more prevalent in patients with hemodialysis: comparison with the findings of multidetector-row computed tomography. Am J Kidney Dis. 2006;48(2): Akahori H, Uematsu M, Morozumi T, et al. Magnitude of the improvement in skin perfusion pressure is as important as skin perfusion pressure immediately following intervention for predicting limb salvage in critical limb ischemia. Presented at: 56th Annual Scientific Session of the American College of Cardiology; March 2007; New Orleans, LA. 23. Shimazaki M, Matsuki T, Yamauchi K, et al. Assessment of lower limb ischemia with measurement of skin perfusion pressure in patients on hemodialysis. Ther Apher Dial. 2007;11(3): Iida O, Nanto S, Uematsu M, Morozumi T, Akahori H, Nagata S. Endovascular therapy for limb salvage in a case of critical lower limb ischemia resulting form fibromuscular dysplasia. J Vasc Surg. 2007;46(4): WOUNDS