Predictive value of transcutaneous oxygen pressure and amputation success by use of supine and elevation measurements J. Michael Bacharach, MD, Thom W. Rooke, MD, Philip J. Osmundson, MD, and Peter Gloviczki, MD, Rochester, Minn. The purpose of this study was to determine if transcutaneous oxygen pressure (tcpo2) measurements can be used to predict amputation site healing in lower limbs with arterial occlusive disease. We measured tcp02 (supine and with limb elevation) in 90 limbs before amputation and reviewed their subsequent clinical course. Of these, 52 (57%) successfully healed, 21 (23%) failed, and 17 (18%) exhibited delayed healing. Limbs with delayed healing or failure had significantly lower tcpo 2 values than values of those that healed. A tcpo 2 > 40 torr was associated with primary or delayed healing in 51 of 52 limbs (98%), and a tcpo 2 value of < 20 tort was universally associated with failure. For patients with a tcpo2 between 20 and 40 torr, tcpo 2 measurements obtained during limb elevation improved the predictability of outcome. We conclude that supine tcpo 2 measurements can help predict amputation site healing, and that tcpo 2 measurement during limb elevation improves predictability in limbs with borderline supine tcpo 2 values. (J VAsc SURG 1992;15:558-63.) Despite numerous interventions and improved vascular surgical techniques, the vascular clinician continues to be confronted with the patient facing amputaticn because of severe peripheral vascular disease. The decision to amputate is usually made only after other therapeutic options have been exhausted. Determining the correct level at which to perform the amputation is extremely important for (1) maximizing the patient's rehabilitation potential, and (2) preventing surgical revisions or a second amputation at a more proximal site. n the past, clinicians have used features of the physical examination including color, temperature, peripheral pulses, and wound edge bleeding to assess the potential for healing at a particular level. These clinical criteria are clearly helpful but alone have significant limitations in predicting healing. Over the years numerous techniques and laboratory methods have been tested as means to augment physical examination in predicting amputation site healing. Transcutaneous oximetry (tcp02) has been promoted by many as a reproducible noninvasive From the Division of Cardiovascular Diseases and the Division of Vascular Surgery, Mayo Clinic, Rochester. Reprint requests: J. Michael Bacharach, MD, Division of Cardiovascular Diseases, Mayo Clinic and Mayo Foundation, Rochester, MN 55905. 24/1/32728 technique for measuring limb ischemia; however, no consensus exists as to a threshold level that predicts amputation site healing or failure. To further confuse matters it has recently been suggested that tcpo 2 measurements are not helpful in predicting amputation site healing.1 The purpose of this study was to review the Mayo Clinic's experience in using tcpo 2 measurements to predict healing versus nonhealing at a specific site of amputation. We attempted to determine the tcpo 2 threshold level that could reliably predict healing versus nonhealing. PATENTS AND METHODS All of the patients identified for this study group had known peripheral vascular disease and underwent specific preamputation noninvasive vascular laboratory studies, including tcpo2 measurements. The data were collected at a time when tcpo2 measurements were still investigational in our laboratory. As a result of this investigational status, the tcpo 2 information was not made available to the clinician making the decision about amputation healing or level. Transcutaneous oxygen is measured with an oxygen sensor consisting of two parts: (1) a modified Clark-type polarographic sensor, a silver anode, electrolyte, and an oxygen permeable membrane; and 558
Volume 15 Number 3 March 1992 Supine and elevation tcpo 2 measurements 559 (2) a heating section with two precision thermistors for measuring and controlling the sensor temperature. When the sensor is subjected to oxygen, the oxygen molecules diffuse through the membrane and create an electrochemical reaction that causes current to flow through the cathode. An amplifier connected to the cathode measures the amount of current flowing and converts it to a value proportional to the oxygen tension at the sensor/membrane interface. This information is displayed as tcpo 2. n our laboratory we use the Novametric Model 811 (Novametrix Medical Systems, nc., Wallingfort, Conn.). Before patient monitoring, a "zero" and "highpoint" calibration are performed. This procedure uses a zero oxygen solution to allow calibration of the zero point and ambient oxygen (room air) to allow for high-point calibration. The high-point calibration can vary considerably because the partial pressure of oxygen in room air is dependent on room temperature, relative humidity, and barometric pressure. For calibration purposes we used a barometric pressure estimate of 730 mm Hg, which is standard for geographic location. With a room temperature of 24 to 26 C and assuming 50% relative humidity, our machines calibrate at 150 mm Hg as the high-point (room air) calibration. The machines are allowed to equilibrate for a minimum of 30 minutes before testing, and the electrode membrane is maintained at 45 C. Once the electrode is placed on the patient, an additional 20 minutes is allowed for equilibration before taking any measurements. For this study tcpo 2 measurements were obtained by use of a variation of the standard protocol that we have previously described, z Electrodes were placed along the limb (1) on the dorsum of the foot over the metatarsals, (2) 4 cm above the medial malleolus, (3) 8 cm below the knee, and (4) 10 cm above the knee, and steady-state surface oxygen measurements were initially made with the patient lying supine and then repeated after elevation of the lower extremities to 30 C for 3 minutes. The electrode surface temperature was kept at 45 C throughout the study. nformation was collected from patients' hospital and clinic charts. Additional follow-up via return clinic visits and written or telephone inquiries was obtained. Data were collected on clinical outcome after amputation, extent of healing, and the time course of heating after operation. For study purposes we considered the site of amputation to have healed successfully if the wound closed and healed within 6 weeks after surgery. Amputations were characterized as having delayed healing if healing occurred beyond 6 weeks with or without local debridement procedures. Amputations that required revisions at a higher level were defined as failures. The following electrode placement sites were used to obtain tcpo 2 values for the corresponding amputation levels: thigh placement for above-theknee amputations, calf for below-the-knee amputations, and foot for transmetatarsal and Syme's amputations. n addition to the amputation data, demographic information regarding the patient's age, sex, smoking status, presence of diabetes, and presence of hypertension were also collected; these data serve to further define the study population (Table ). To determine the significance of the differences in (1) supine tcpo 2 values, and (2) the change in tcpo 2 value with leg elevation between the healed failed and delayed healing groups, unpaired Student's t tests were performed. Values forp of less than 0.05 were considered significant. Sensitivity and specificity were analyzed by use of the standard mathematic formulas. A true-positive test result was defined as an amputation site that failed with the tcpo 2 value predicting failure, and a true-negative result was defined as an amputation site healing with the tcpo 2 value predicting healing. The criteria used for the positive and negative predictions of healing are summarized in Table. RESULTS During the period July 1, 1988, to Dec. 31, 1989, 75 patients undergoing a total of 90 amputations underwent preoperative tcpo 2 studies. Of these amputations, 52 (58%) were below-the-knee, 25 (28%) were above-the-knee, 11 (12%) were metatarsal amputations, and 2 (2%) were Syme's amputations. Fig. 1 represents a cumulative summary of supine tcpo 2 values for all 90 amputations according to amputation outcome. n analyzing all observed amputations, independent of site, 52 (58%) amputanons successfully healed, 21 (23%) amputations failed, and 17 (18%) amputations exhibited delayed healing. For the healed group the mean tcpo 2 value was 51 torr; in the delayed healing group the mean tcpo 2 value was 33 torr; and in the failed group the mean tcpo 2 value was 14 torr. Unpaired t tests comparing the healed to failed groups and the healed to delayed healing groups demonstrated statistical significance (p < 0.001). n our study a tcpo 2 measure of 40 torr or greater was predictive of healing. We did not observe primary healing in patients with a supine tcpo 2 of less
560 Bacharach et al. Journal of VASCULAR SURGERY Q. 20 ; 'X A,~.. m Healed Delayed Failed Fig. 1. Supine tcpo 2 values by amputation outcome for all 90 observed amputations. Table. Patients studied No. of patients Total no. of amputations Mean age (yr) Sex Clinical risk factors Smoking status (current or past 48/75 (64%) smokers) Diabetes 44/75 (58%) Hypertension 39/75 (52%) than 30 torr, and a tcpo 2 value of less than 20 torr was universally associated with amputation failure. Sensitivity and specificity for all amputations with the use of the criteria of a positive test (supine tcpo 2 of less than 20 torr) or negative test (supine tcpo 2 greater than 40 torr) demonstrated a 70% sensitivity and an 88% specificity. The positive predictive value was 64%, with a negative predictive value equal to 91%. Of the patients with tcpo 2 values of 20 to 40 torr, outcome was variably divided between failure, successful healing, and delayed heating. Further analysis of this group by use of tcpo 2 with leg elevation revealed that in the healed group the mean decrease in tcpo 2 in response to elevation was 4.0 torr, in the delayed healing group the mean decrease was 9.4 torr, and in the failed group the mean decrease in tcpo 2 was 14.8 torr (Fig. 2). The difference between the healed and failed groups was statistically significant (p = 0.0265); after pooling the healed and delayed healing limbs into a single group, the difference between this "combined" group Table. Criteria used for positive and 75 negative predictions of healing 90 67 range 25-88 Positive test (amputation failure) 48 (64%) men TP Amputation failure with a supine tcpo2of < 20 torr 27 (36%) women or a decrease in tcpo 2 of > 15 torr in response to 3 minutes of leg elevation TN Healed amputation with a supine tcpo 2 of _> 20 torr or a decrease in tcpo 2 of < 15 torr in response to 3 minutes of leg elevation FN Amputation failure with a supine tcpo 2 of _> 20 torr or a decrease in tcpo 2 of < 15 torr in response to 3 minutes of leg elevation FP Healed amputation with a supine tcpo 2 of < 20 torr or a decrease in tcpo 2 of > 15 torr in response to 3 minutes of leg elevation and the failed group just missed statistical significance (p = 0.0575). The sensitivity and specificity of tcpo 2 values for patients with supine tcpo2s of 20 to 40 torr were calculated with the criteria of a positive test (observed decrease in tcpo 2 of greater than 15 torr in response to 3 minutes of leg elevation) or negative test (observed decrease in tcpo 2 of less than 15 torr in response to 3 minutes of leg elevation). Sensitivity was equal to 60%, with a specificity of 89%. The positive predictive value was 60%, with a negative predictive value of 89%. When the parameters of supine and leg elevation tcpo 2 measures were both applied to the entire amputation population, sensitivity and specificity improved. The combined sensitivity was equal to 85%, with a specificity of 97%. The positive predictive value was 89%, with a negative predictive value of 96%.
Volume 15 Number 3 March 1992 Supine and elevation tcpo 2 measurements 561 40 - m m 30 0,1 0 fl- 20 0-10 Supine Elevated Healed Mean ~ = 4.0 Supine Elevated Delayed Mean ~ = 9.2 Supine Elevated Failed Mean ~ = 14.8 Fig. 2. Change in tcpo 2 values in response to leg elevation by amputation outcome for 29 patients with borderline tcpo 2 Values of between 20 to 40 torr. DSCUSSON Recognition that clinical criteria alone have limitations in predicting amputation success has led to numerous efforts to find a complementary technique that would aid in more accurately predicting amputation site healing. Numerous laboratory studies such as segmental blood pressure, skin blood pressure, clearance of xenon ~33, and tcpo 2 measurements have been reviewed, and, of these various methods, tcpo 2 measurements emerge as a relatively simple and reproducible technique that has potential usefulness in studying amputation site healing. 3-~ A number of studies evaluating tcpo 2 as a predictor of amputation site healing have been done, 6-~s and, in general, tcpo 2 was deemed to be a reliable predictor of heating, although absolute levels at which healing will or will not occur have not been uniformly established. The matter is not, however, without controversy. Recently, Falstie-lensen et al. ~ published data suggesting that tcpo 2 measurements were not helpful in the selection of lower limb amputation level. Our results provide further support that tcpo 2 measurements have clinical utility in the assessment of amputation level. Based on our data, an amputation, regardless of site, with a tcpo 2 value less than 20 torr has a high probability of failttre. Transcutaneous oxygen pressure values above 40 torr are predictably associated with healing. f the tcpo 2 value falls into our defined borderline zone of 20 to 40 torr, measuring the tcpo 2 Values after leg elevation improves the predictability of outcome. Other studies have evaluated the relationship between tcpo 2 and amputation healing. Matsen et al.3 concluded that tcpo 2 values of less than 24 mm Hg were associated with a poor probability of primary healing. Franzeck et al)2 evaluated the predictive value of tcpo 2 for successful amputation and proposed an initial threshold value of 10 mm Hg. n evaluating tcpo 2 measurements in the limbs of diabetic and nondiabetic patients with peripheral vascular disease, Wyss et al. s concluded that tcpo 2 values below 20 mm Hg were significantly more likely to have ulcers, rest pain, or require amputation, as compared with limbs in which tcpo 2 values were above 20 mm Hg. s Byrne et al.14 concluded that tcpo 2 levels in excess of 38 mm Hg were uniformly associated with healing, whereas levels below 38 mm Hg were associated with outright failure or significandy delayed healing. Ratliff et al.7 demonstrated that tcpo 2 values in patients undergoing amputation were significantly lower in failed versus healed amputations irrespective of site. These results suggested that a value of above 35 mm Hg was associated with healing, and failure was associated with 35 mm Hg or less. Oishi et al? s found that tcpo 2 measurement was the most accurate predictor of successful healing of an
562 Bacharach et al. Journal of VASCULAR SURGERY amputation. Ameli et al.n further validated tcpo 2 as a predictor of primary healing after amputation, although their study did not attempt to define a threshold tcpo 2 value. Wyss et al. 8 demonstrated a predictive value for tcpo 2 values and amputation site healing in distal limb amputations but little or no predictive value for healing in above the knee amputations. Kram et al. 9 demonstrated that tcpo 2 values were significantly lower in patients with unsuccessful wound healing after below-knee amputation. Their data indicated that successful wound healing was much greater iftcpo 2 values were greater than 20 torr; however, 50% of the patients with absolute tcpo 2 values less than 20 torr also healed. By calculating a critical Po 2 index using calf/brachial tcpo 2 ratios, they substantially improved predictive accuracy. n assessing predictive value of tcpo 2 for amputation site healing, most of these studies attempted to establish a "critical" or threshold value that would be specific for healing or nonhealing. Although a predictive range appears to exist, none of these studies, including our own, can establish an absolute or "critical value." The predictive ranges differ considerably, and there is a lack of consensus between studies despite validation that tcpo 2 measurements have predictive value. Some of this variation can be explained in testing method. The absolute tcpo 2 values are influenced by many technical features: (1) the type of equipment and instrumentation used, (2) the duration of time for equilibration, (3) electrode placement, and (4) electrode surface temperature. Electrode surface temperature may be the most critical. Rooke et al) 6 demonstrated that tcpo 2 measurements can vary significantly with electrode temperature; measuring tcpo 2 values at an electrode temperature of 45 C provides for maximal vasodilation. Measuring tcpo 2 values at lower skin temperattires allows blood vessels to maintain their reactivity to vasoactive stimuli resulting in lower tcpo 2 values. n the above cited studies, electrode and skin temperatures varied from 43 C to 45 C; this small difference in electrode temperature can substantially alter the observed tcpo 2 values and can explain much of the variation in tcpo 2 values between studies. Modifications, such as measurement of the change in tcpo 2 after inhalation of oxygen (Oisihi et al.15) or the use of mathematic indexes of limb tcpo 2 compared to brachial or chest tcp02, have been used to improve the predictive accuracy of the test. Although they are to some degree successful, they fall short of providing a means to more accurately assess those patients who fall into a borderline category. The major significance of our data is the demonstrated value of supine tcpo 2 measurements in predicting amputation site healing. The addition of tcpo 2 measurement during elevation provides a method by which to assess patients in the borderline area (tcpo 2 20 to 40 torr) and predict amputation outcome in this subset of patients, in whom supine tcp% measurements alone are not predictive. Substantial data exist confirming the value of tcpo 2 measurement in limbs before amputation. t is also well recognized that amputation success or failure is complex and dependent on numerous factors. Clinical criteria of tissue ischemia along with the patient's general status are extremely important. Measurement of tcpo 2 provides additional means of evaluating tissue perfusion that can be included in the overall prediction of successful wound healing. The leg elevation method for tcpo 2 value provides an important adjunct in assessing the patient whose condition is borderline and in improving the accuracy with which wound healing can be predicted. REFERENCES 1. Faltsie-Jensen N, Christensen KS, Brochner-Mortenson J. Selection of lower limb amputation level not aided by transcutaneous Po 2 measurements. Acta Orthop Scand 1989; 60:483-5. 2. Osmundson PJ, Rooke TW, Hallett JW. Effect of arterial revascularization on transcutaneous oxygen tension of the ischemic extremity. Mayo Clin Proc 1988;63:897-902. 3. Matsen FA, Wyss CR, Pedegana LR, et al. Transcutaneous oxygen tension measurements in peripheral vascular disease. Surg Gynecol Obstet 1980;150:525-8. 4. Rooke TW, Osmundson PJ. Variability and reliability of transcutaneous oxygen tension measurements in the assessment of peripheral vascular disease. Angiology 1989;40:695-700. 5. Hodgson KJ, Somne DS. Noninvasive assessment of lower extremity arterial disease. Ann Vasc Surg 1988;2:174-84. 6. Burgess EM, Matsen FA. Determining amputation levels in peripheral vascular disease. Am J Bone Joint Surg 1981;63: 1493-6. 7. Ratliff DA, Clyne CAC, Chant ADB, et al. Prediction of amputation wound healing: the role of transcutaneous Po 2 assessment. Br J Surg 1984;71:219-22. 8. Wyss CR, Harrington RM, Burges EM, et al. Transcutaneous oxygen tension as a predictor of success after an amputation. J Bone Joint Surg 1988;70-A:203-7. 9. Kram HB, Appel PL, Shoemaker WC. Multisensor transcutaneous osimetric mapping to predict below knee amputation wound healing: use of critical Po z. J VASC SURG 1988;9:796-800. 10. Lusiani L, Visona A, Nicolin P, et al. Transcutaneous oxygen tension (tcpo2) measurement as a diagnostic tool in patients with peripheral vascular disease. Angiology 1988;39: 873-80.
Volume 15 Number 3 March 1992 Supine and elevation tcpo 2 measurements 563 11. Ameli FM, Byrne P, Provan JL. Selection of amputation level and prediction of healing using transcutaneous tissue oxygen tension (tcpo2). J Cardiovasc Surg 1989;30:220-4. 12. Franzek FK, Talke P, Bernstein EF, et al. Transcutaneous Po 2 measurements in health and peripheral arterial occlusive disease. Surgery 1982;91:156-63. 13. Wyss CR, Matsen FA, Simmons BS, Burgess EM. Transcutaneous oxygen tension measurements on limbs of diabetic and non-diabetic patients with peripheral vascular disease. Surgery 1984;95:339-45. 14. Byrne P, Provan JL, Ameli FM, et al. The use of transcutaneous oxygen tension measurements in the diagnosis of peripheral vascular insufficiency. Ann Surg 1984;200:159-65. 15. Oishi CS, Fronet A, Golbranson FL. The role of noninvasive vascular studies in determining levels of amputation. J Bone Joint Surg 1988;70-A:1520-30. 16. Rooke TW, Hollier LH, Osmundson PJ. The influence of sympathetic nerves on transcutaneous oxygen tension in normal and ischemic lower extremities. Angiology 1987;38: 400. Submitted Mar. 22, 1991; accepted July 25, 1991.