- Email: [email protected]
Is there a critical level of plantar foot pressure to identify patients at risk for neuropathic foot ulceration?
Is There a Critical Level of Plantar Foot Pressure to Identify Patients at Risk for Neuropathic Foot Ulceration? David G. Armstrong, DPM, Edgar J. G. Peters, Kyriacos A. Athanasiou, PhD, PE, and Lawrence A. Lavery, DPM The purpose of this study was to identify a point along the spectrum of peak plantar forefoot pressure that has an optimum combination of sensitivity and specificity to screen for neuropathic ulceration. We enrolled 219 diabetic patients in this case-control study in an approximate 2:1 control:case ratio. Cases were defined as patients with an active or recently healed neuropathic ulceration. Controls were defined as those with no history of ulceration. All patients had peak plantar pressures analyzed with the EMED gait analysis system. Peak plantar pressure was, as expected, significantly higher for patients with ulcers compared to controls [83.1 ±24.7N/cm2 (range, 10-125) vs. 62.7 ±24.4 N/cm 2 (range, 7.3-113), p < .001]. The ulcer group was clearly skewed toward a higher prevalence of elevated peak plantar forefoot pressure compared with the control group, which displayed the opposite trend (control group skewness = 0.286, kurtosis = -0.482; ulcer group skewness = -0.389, kurtosis = -0.289). Using receiver operating characteristic analysis, the optimal cut-point, as determined by a balance of sensitivity and specificity was 70 Nicm", which yielded a sensitivity of 70.0% and a specificity of 65. 1 %. We concluded that, while there is no optimal cut-point for clearly screening patients for risk of foot ulceration, the higher the peak pressure, the higher the commensurate risk. (The Journal of Foot & Ankle Surgery 37(4):303-307,1998) Key words: amputation, diabetes mellitus, pressure, ulceration
Diabetes continues to be the most common single underlying cause of lower extremity amputation in the United States and Europe. Fifty to 80% of all lower extremity amputations occur in persons with diabetes (1-3). In this population, amputation is commonly associated with a high rate of reamputation (4, 5), amputation of the contralateral leg (5-7), and death during hospitalization and in the ensuing 3- 5 years following the amputation (8, 9). In addition, for as many as one quarter of amputees, amputation is a pivotal event leading to placement in a nursing home or extended health care facility and a significant demise in the amputee's quality of life and independence (10, II). Fortunately, many amputations can be prevented. Several studies in both the United States and United Kingdom have demonstrated dramatic reductions in From the Department of Orthopaedics , University of Texas Health Science Center , San Antonio , TX and The Diabetic Foot Research Group, and the Mexican American Medical Treatment Effectiveness Research Center, San Antonio, TX. Address correspondence to: D. G. Armstrong, DPM, Assistant Professor, Department of Orthopaedics, the University of Texas Health Science Center, San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78284-7776. Received for publication January 1998; accepted in revised form for publication April 1998. The Journal of Foot & Ankle Surgery 1067-2516/98/3704-0303$4.00/0 Copyright © 1998 by the American College of Foot and Ankle Surgeons
diabetes-related amputations when a multispecialty approach to diabetes and the diabetic foot is utilized (12-14). Foot ulceration is one of the most common components in the causal pathway to limb loss, and therefore treatment and prevention of ulcers is the central focus of amputation prevention programs (15, 16). Neuropathic ulcers usually develop at areas on the sole of the foot exposed to moderate to high repetitive pressures during the course of normal walking (17). Over an extended period of time, this type of repetitive injury results in inflammation, focal tissue ischemia, necrosis, and ulceration that develops and progresses unrecognized by diabetic persons with sensory neuropathy. Subjects with neuropathy, but without a portal for entry of bacteria, rarely develop infections, and therefore, in the absence of critical ischemia, rarely require amputations (15). In an era of rationed care and increasing disease prevalence, there is a growing need for better criteria to identify high-risk patients in order to allocate scarce resources such as therapeutic footwear, prosthetics, and clinic visits. Because abnormal foot pressures have been strongly linked to the development and rate of healing of foot ulcers , this has become one of the focus areas of investi gation and treatment. Boulton and associates evaluated barefoot pressures in neuropathic and non-neuropathic diabetic patients and found that pressures were greater VOLUME 37, NUMBER 4, JULY/AUGUST 1998
303
TABLE 1
Descriptive characteristics
Group
No ulcer Neuropathic ulcer
N
Age (yr)
149 70
51.8 ± 10.4 52.3± 10.3
% Male
Duration of OM (yr)
A81
TCP02 (mmHg)
8MI
33 74*
9.2 ± 8.8 14.3 ± 9.2*
0.99 ± 0.16 0.96 ± 0.17
41.0±13.9 46.0 ± 18.8
32.3±6.2 30.9 ± 5.7
*p < .05. All values are mean ± standard deviation. 8MI = body mass index; TCP02 = transcutaneous oxygen tension; A81 = ankle-brachial systolic pressure index. Six patients with nonweightbearing ulcers were excluded from analysis from the original 76 cases.
than 110 N/cm 2 for every subject with a foot ulcer, suggesting a threshold pressure below which individuals would not ulcerate. Only 31 % of diabetic subjects without a history of ulceration demonstrated abnormal peak foot pressures based on Boulton's criteria (18). However, it is not clear if a threshold pressure level exists since other reports have identified lower peak foot pressures at sites of neuropathic ulceration (17) than those identified by Boulton (15, 17, 19). For instance, diabetic subjects with peak plantar pressures above 65 Nzcm? have been shown to be at six times greater risk for ulceration than those with pressures below this value (15). Clearly, identification of an optimal peak plantar pressure cut-point to help physicians stratify diabetics by risk would be a valuable tool. Therefore, the purpose of this paper was to identify a point along the spectrum of peak plantar forefoot pressure that has an optimum combination of sensitivity and specificity to screen for neuropathic ulceration. Methods
This project was conducted as a case-control study at the Texas Diabetes Institute and The University of Texas Health Science Center Clinics at San Antonio. The Texas Diabetes Institute is a model program for multidisciplinary diabetes care and includes core participation of general internal medicine, endocrinology, ophthalmology, podiatry, diabetes nurse education, and social services. Following informed consent, all patients were enrolled sequentially from these clinics. Prior to recruitment, institutional review board approval was secured at this institution. The authors analyzed data from 76 cases and 149 controls that were diagnosed with diabetes mellitus based on World Health Organization criteria (20). Cases were defined as patients with an existing or a recently healed «4 weeks) foot ulceration (21). For the purposes of this analysis, only patients with plantars wounds were included. Six subjects with nonweightbearing ulcers were excluded. Controls were defined as subjects who had never had a foot ulceration. The authors assessed peripheral sensory neuropathy using vibration perception threshold (VPT) testing at the distal great toe using a Biothesiometer 304
THE JOURNAL OF FOOT & ANKLE SURGERY
(22,23).1 "Loss of protective sensation" was defined using the criteria described by Armstrong and co-workers (a vibration perception threshold greater than 25 V) (22). Patients with ulcers on the ankle or leg were eliminated from the study. Lower extremity peripheral vascular status was evaluated using transcutaneous oxygen tension on the dorsal aspect of the first intermetatarsal space (24), and ankle-brachial systolic blood pressure index (25). Descriptive statistics for this population are summarized in Table 1. Diabetes was stratified into type I or II, based on the algorithm described by Mogensen (26). The authors used the EMED pressure platform system to evaluate dynamic barefoot pressures on the sole of the foot pressures (27).2 The system measures pressures at a resolution of approximately 4 pixels per square centimeter over the entire surface of contact. The location and value of the largest (peak) focal pressure was recorded. This peak pressure was averaged from three recorded midgait steps on the EMED pressure platform. For selecting the optimal diagnostic cutoff points on the scale of measurement, receiver operating characteristics (ROC) curves were employed (22, 28, 29). A t-test was used for independent samples to evaluate the difference between continuous variables between groups and a chi-squared test with a 95% confidence interval was used to evaluate dichotomous variables. All values are expressed as mean ± standard deviation (30). Results
There was no significant difference in age, vascular perfusion, or body mass index between the case and control groups. Subjects with neuropathic ulceration had a significantly longer duration of diabetes than controls (41.0 ± 13.9 vs. 8.1 ± 7.4, p < .001). Males were more prevalent in the ulcer group as well (74% vs. 33%, X 2 = 33.7, p < .001). Peak plantar pressure was, as expected, significantly higher for patients with ulcers compared to controls [83.1 ± 24.7 Nzcm? (range, 10-125) vs. 62.7 ± 1
2
Biomedical Instrument Company, Newbury, OH. Novel Electronics, St. Paul, MN.
40
Conclusions
······ · No Ulcer
r>.
35
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-
10
Neu-opathic Ulcer
+--~~------',--..lr-
5+--.,,...:-+-- - - - ----'- -\-0-20
2 1 ~O
41-60
6 1-80
81-100 101·120
>120
Pressure (N/cm2 )
Distribution of plantar pressures by group.
FIGURE 1
21.4 N/cm 2 (range, 7.3-113), p < .001]. Figure 1 illustrates the distribution of plantar pressures in both patients with and without ulcers. The ulcer group was clearly skewed toward a higher prevalence of elevated peak plantar forefoot pressure compared with the control group, which displayed the opposite trend (control group skewness = 0.286, kurtosis = 0.482; ulcer group skewness = 0.389, kurtosis = 0.289). Results of the receiver operating characteristic analysis (ROC) are summarized in Fig. 2. As expected, cut-points delineated at relatively low plantar pressures were very sensitive for detecting risk of neuropathic ulceration, but very nonspecific (35 N/cm 2 = 98.6% sensitivity, 6.7% specificity). Conversely, cut-points made at high plantar pressures were very specific for screening for risk of ulceration, but not very sensitive (110 N/cm 2 = 15.7% sensitivity, 98.0% specificity). The optimal cut-point, as determined by a balance of sensitivity and specificity was 70 N/cm2 , which yielded a sensitivity of 70.0% and a specificity of 65.1 %.
70 N/cm'
-. -.
• •
•
..
100
•
•
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-
•
-
100
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90 80
110 ~/cm'
70 60 50
.g
40
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~
.g
30 ~ 20 10
35 N/cm 2
o 80
60
40
20
o
% Sensitivity FIGURE 2 pressures.
Receiver operating characteristic curve of peak plantar
The results of this study suggest that persons with diabetes and neuropathic ulcers have significantly higher peak plantar pressures than their nonulcerated diabetic counterparts. Furthermore, this difference may ultimately offer the ability to assess for degree of risk for ulceration when used in conjunction with other contributory risk factors (31, 32). The data indicate that there may be no single point on the spectrum of peak foot pressures that can indicate with certainty when a subject will ulcerate. However, what is clearly suggested is that as peak foot pressures increase, so does the likelihood of ulceration. As other investigators have suggested, it is a combination of factors (neuropathy, foot deformity, limited joint mobility, and abnormal plantar pressures) (15) that ultimately lead to ulceration and amputation. There are three main extrinsic mechanisms of tissue breakdown in the insensitive foot (33). The common link between each of these mechanisms is mechanical stress. These mechanisms include: direct mechanical disruption of tissue (e.g., a foreign body puncturing the skin), prolonged pressure over a small area leading to local ischemia and tissue breakdown (e.g., a bunion deformity precipitating an ulcer on the medial margin of the foot), and repetitive moderate forces leading to inflammation and enzymatic autolysis (e.g., ambulation on an unprotected foot leading to skin breakdown beneath a prominent metatarsal head). This third mechanism is the most common etiology of the plantar diabetic foot ulcer (34). This should come as no surprise, since cyclic loading is the most widely accepted precipitating factor in failure of materials. This phenomenon, termed fatigue, stipulates that the majority of catastrophic failures experienced by a material are due to many cycles of loading at a stress level that is lower than the strength (or maximum stress) of the material. The second and third mechanisms of injury described above are precipitated by two main factors, foot deformity and limited joint mobility, which in tum lead to increased plantar foot pressures. Plantar foot pressures, when elevated, theoretically require less repetitive stress to initiate soft-tissue breakdown. Again, this statement agrees with the concept of fatigue failure, which predicts that the higher the stress level, the smaller the number of cycles that will be required by a material to fail. It, therefore, should come as no surprise that in this study foot ulcers were associated with a higher prevalence of elevated foot pressures. A limitation of this study is the evaluation of total compressive stress as the sole determining mechanical factor. Although this is currently the accepted modality, it should be borne in mind that shear stress and its concomitant strain may be at least equally relevant in determining soft tissues' propensity for breakdown at the VOLUME 37, NUMBER 4, JULY/AUGUST 1998
305
plantar aspect of the foot. Unfortunately, at this time there is not a well accepted, validated devise to measure shear stress and strain in vivo, and the authors were therefore not able to evaluate this variable. Reducing foot pressures on the sole of the foot with therapeutic footwear and prosthetics is pivotal to prevent the development of ulcers in high-risk patients and to heal ulcers once they develop (35). Much of the recent literature in wound healing has focused on expensive, high-tech growth factors and bioengineered tissue with less than sterling results (36). None of these studies seem to have adequately off-loaded the foot, and therefore healing rates were far less than in studies that used prosthetics that have been shown to possess superior pressure reduction capabilities (17, 37 -43). This continues to be an area that needs to be scientifically evaluated in greater detail. Only until we identify and accommodate for high plantar pressure through appropriate shoe gear and prostheses for all insensate diabetic patients (35) will we be able to reduce the unconscionably high number of preventable lower extremity amputations throughout the industrialized and developing world. References 1. Armstrong, D. G., Lavery, L. A., van Houtum, W. H., Harkless, L. B. Seasonal variations in lower extremity amputation. J Foot Ankle Surg. 36:146-150, 1997. 2. Lavery, L. A., Ashry, H. R., van Houtum, W., Pugh, J. A., Harkless, L. B., Basu, S. Variation in the incidence and proportion of diabetes-related amputations in minorities. Diabetes Care 19:48 - 52, 1996. 3. van Houtum, W. H., Lavery, L. A., Harkless, L. B. The impact of diabetes-related lower extremity amputations in the Netherlands. Diabetes and Its Complications 10:325-330, 1996. 4. Armstrong, D. G., Lavery, L. A., Harkless, L. B., van Houtum, W. H. Amputation and reamputation of the diabetic foot. JAPMA 87:255-259, 1997. 5. Murdoch, D. P., Armstrong, D. G., Dacus, J. B., Laughlin, T. J., Morgan, C. B., Lavery, L. A. The natural history of great toe amputations. J Foot Ankle Surg 36:204-208, 1997. 6. Goldner, M. G. The fate of the second leg in the diabetic amputee. Diabetes 9:100-103,1960. 7. Whitehouse, F. W., Jurgenson, c., Black, M. A. The later life of the diabetic amputee. Diabetes 17:520-521, 1968. 8. Lavery, L. A., van Houtum, W. H., Harkless, L. B. In-hospital mortality and disposition of diabetic amputees in the Netherlands. Diabetic Med. 13:192-197, 1996. 9. van Houtum, W. H., Lavery, L. A. Outcomes associated with diabetes-related amputations in the Netherlands and in the State of California, USA. J. Intern. Med. 240:227-231, 1996. 10. Lavery, L. A., van Houtum, W. H., Armstrong, D. G. Institutionalization following diabetes-related lower extremity amputation. Am. J. Med. 103:383-388, 1997. 11. Muecke, L., Shekar, S., Dwyer, D., Israel, E., Flynn, P. G. Functional screening of lower-limb amputees: a role in predicting rehabilitation outcome? Arch. Phys. Med. Rehabi1. 73:851-858, 1992. 12. Edmonds, M. E., Blundell, M. P., Moms, M. E., Thomas, E. M., Cotton, L. T., Watkins, P. J. Improved survival of the diabetic foot: the role of a specialized foot clinic. Q. J. Med. 60:763-771, 1986.
306
THE JOURNAL OF FOOT & ANKLE SURGERY
13. Edmonds, M. E. Experience in a multidisciplinary diabetic foot clinic. In: Connor H Boulton AJM Ward JD, ed. The Foot in Diabetes, pp. 121-131, edited by H. Connor, A. J. M. Boulton, J. D. Ward, Wiley, Chichester, 1987. 14. Runyan, J. W. The Memphis chronic disease program: Comparisons in outcome and the nurses extended role. JAMA 231 :264- 267, 1975. 15. Lavery, L. A., Armstrong, D. G., Vela, S. A., Quebedeaux, T. L., Fleischli, J. G. Practical criteria for screening patients at high risk for diabetic foot ulceration. Arch. Intern. Med. 158:158-162, 1998. 16. Pecoraro, R. E., Reiber, G. E., Burgess, E. M. Pathways to diabetic limb amputation: Basis for prevention. Diabetes Care 13:513-521, 1990. 17. Armstrong, D. G., Lavery, L. A., Bushman, T. R. Peak foot pressures influence healing time of diabetic ulcers treated with total contact casting. J. Rehabi1. Res. Dev. 35:1-5,1998. 18. Boulton, A. J. M., Connor, H., Hardisty, C. A., et a1. Dynamic foot pressure and other studies as diagnostic and management aids in diabetic neuropathy. Diabetes Care 6:26, 1983. 19. Boulton, A. J. M., Hardisty, C. A., Belts, R. P., Franks, C. 1., Worth, R. C., Ward, J. D., Duckworth, T. Dynamic foot pressure and other studies as diagnostic and management aids in diabetic neuropathy. Diabetes Care 6:26-33, 1983. 20. World Health Organization. Second Report on Diabetes Mellitus, World Health Organization, Geneva, 1980. 21. Armstrong, D. G., Lavery, L. A., Harkless, L. B. Validation of a diabetic wound classification system: the independent contribution of depth, infection, and vascular disease to the risk of amputation. Diabetes Care 21:855-859, 1998. 22. Armstrong, D. G., Lavery, L. A., Vela, S. A., Quebedeaux, T. L., Fleischli, J. G. Choosing a practical screening instrument to identify patients at risk for diabetic foot ulceration. Arch. Intern. Med. 158:289-292, 1998. 23. Young, M. J., Breddy, J. L., Veves, A., Boulton, A. J. M. The prediction of diabetic neuropathic foot ulceration using vibration perception thresholds. Diabetes Care 16:557 - 560, 1994. 24. McNeely, M. J., Boyko, E. J., Ahroni, J. E., Stensel, V. L., Reiber, G. E., Smith, D. G., Pecoraro, R. E. The independent contributions of diabetic neuropathy and vasculopathy in foot ulceration. Diabetes Care 18:216-219, 1995. 25. Beach, K. W., Strandness, D. E. Arteriosclerosis obliterans and associated risk factors in insulin-dependent and non-insulin dependent diabetes. Diabetes 29:882-888, 1980. 26. Mogensen, C. E. Renoproductive role of ACE inhibitors in diabetic nephropathy. Br. Heart J. 72 (Suppl):38-45, 1994. 27. Graf, P. M. The EMed system of foot pressure analysis. Clin. Pod. Med. Surg. 10:445-454, 1993. 28. Bortheiry, A. L., Malerbi, D. A., Franco, L. J. The ROC curve in the evaluation of fasting capillary blood glucose as a screening test for diabetes and IGT. Diabetes Care 11:1269-1272, 1994. 29. Tsuji, L., Nakamoto, K., Hasegawa, T., Gohdes, D. M., Inawashiro, H., Fukao, A. Receiver operating characteristic analysis on fasting plasma glucose, HbAlc, and fructosamine on diabetes screening. Diabetes Care 14:1075 -1077, 1992. 30. Kirkwood, B. R. Essentials of Medical Statistics, Blackwell, Oxford, 1988. 31. Armstrong, D. G., Lavery, L. A., Harkless, L. B. Treatment-based classification system for assessment and care of diabetic feet. J. Am. Podiatr. Med. Assoc. 86:311-316,1996. 32. Armstrong, D. G., Lavery, L. A. Elevated peak plantar pressure in patients who have Charcot arthropathy. J. Bone Joint Surg. 80A:365-369, 1998. 33. Hall, O. c., Brand, P. W. The etiology of the neuropathic plantar ulcer. J. Am. Podiatry Assoc. 69:173-177,1979.
34. Tredwell, J. Pathophysiology of tissue breakdown in the diabetic foot. In Medical and Surgical Management of the Diabetic Foot, pp. 97 - 112, edited by S. J. Kominsky, Mosby-Year Book, St. Louis, MO, 1994. 35. Lavery, L. A., Vela, S. A., Fleischli, J. G., Armstrong, D. G., Lavery, D. C. Reducing plantar pressure in the neuropathic foot: a comparison of footwear. Diabetes Care 20: 1706 - 1710, 1997. 36. Gentzkow, G. D., Iwasaki, S. D., Hershon, K. S. Use of dermagraft, a cultured human dermis, to treat diabetic foot ulcers. Diabetes Care 19:350-354, 1996. 37. Walker, S. C, Helm, P. A., Pulliam, G. Total contact casting and chronic diabetic neuropathic foot ulcerations: Healing rates by wound location. Arch. Phys. Med. Rehabil. 68:217-221,1987. 38. Walker, S. C, Helm, P. A., Pulliam, G. Chronic diabetic neuropathic foot ulcerations and total contact casting: Healing effectiveness and outcome probability (abstr.). Arch. Phys. Med. Rehabil. 66:574, 1985.
39. Lavery, L. A., Armstrong, D. G., Walker, S. C Healing rates of diabetic foot ulcers associated with midfoot fracture due to Charcot's arthropathy. Diabetic Med. 14:46-49, 1997. 40. Lavery, L. A., Vela, S. A., Lavery, D. C., Quebedaux, T. L. Reducing dynamic foot pressures in high risk diabetics with foot ulcerations: a comparison of treatments. Diabetes Care 19:818-821, 1996. 41. Mueller, M. J., Diamond, J. E., Sinacore, D. R., Blair, V. P., Drury, D., Rose, S. J. Total contact casting in treatment of diabetic plantar ulcers. Diabetes Care 12:384-387, 1989. 42. Sinacore, D. R., Mueller, M. J., Diamond, J. E. Diabetic plantar ulcers treated by total contact casting. Phys. Ther. 67: 1543-1547, 1987. 43. Chantelau, E., Breuer, D., Leisch, A. C, Tanudjada, T., Reuter, M. Outpatient treatment of unilateral diabetic foot ulcers with 'half shoes'. Diabetic Med. 10:267-270, 1993.
VOLUME 37, NUMBER 4, JULY/AUGUST 1998
307
Diabetes continues to be the most common single underlying cause of lower extremity amputation in the United States and Europe. Fifty to 80% of all lower extremity amputations occur in persons with diabetes (1-3). In this population, amputation is commonly associated with a high rate of reamputation (4, 5), amputation of the contralateral leg (5-7), and death during hospitalization and in the ensuing 3- 5 years following the amputation (8, 9). In addition, for as many as one quarter of amputees, amputation is a pivotal event leading to placement in a nursing home or extended health care facility and a significant demise in the amputee's quality of life and independence (10, II). Fortunately, many amputations can be prevented. Several studies in both the United States and United Kingdom have demonstrated dramatic reductions in From the Department of Orthopaedics , University of Texas Health Science Center , San Antonio , TX and The Diabetic Foot Research Group, and the Mexican American Medical Treatment Effectiveness Research Center, San Antonio, TX. Address correspondence to: D. G. Armstrong, DPM, Assistant Professor, Department of Orthopaedics, the University of Texas Health Science Center, San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78284-7776. Received for publication January 1998; accepted in revised form for publication April 1998. The Journal of Foot & Ankle Surgery 1067-2516/98/3704-0303$4.00/0 Copyright © 1998 by the American College of Foot and Ankle Surgeons
diabetes-related amputations when a multispecialty approach to diabetes and the diabetic foot is utilized (12-14). Foot ulceration is one of the most common components in the causal pathway to limb loss, and therefore treatment and prevention of ulcers is the central focus of amputation prevention programs (15, 16). Neuropathic ulcers usually develop at areas on the sole of the foot exposed to moderate to high repetitive pressures during the course of normal walking (17). Over an extended period of time, this type of repetitive injury results in inflammation, focal tissue ischemia, necrosis, and ulceration that develops and progresses unrecognized by diabetic persons with sensory neuropathy. Subjects with neuropathy, but without a portal for entry of bacteria, rarely develop infections, and therefore, in the absence of critical ischemia, rarely require amputations (15). In an era of rationed care and increasing disease prevalence, there is a growing need for better criteria to identify high-risk patients in order to allocate scarce resources such as therapeutic footwear, prosthetics, and clinic visits. Because abnormal foot pressures have been strongly linked to the development and rate of healing of foot ulcers , this has become one of the focus areas of investi gation and treatment. Boulton and associates evaluated barefoot pressures in neuropathic and non-neuropathic diabetic patients and found that pressures were greater VOLUME 37, NUMBER 4, JULY/AUGUST 1998
303
TABLE 1
Descriptive characteristics
Group
No ulcer Neuropathic ulcer
N
Age (yr)
149 70
51.8 ± 10.4 52.3± 10.3
% Male
Duration of OM (yr)
A81
TCP02 (mmHg)
8MI
33 74*
9.2 ± 8.8 14.3 ± 9.2*
0.99 ± 0.16 0.96 ± 0.17
41.0±13.9 46.0 ± 18.8
32.3±6.2 30.9 ± 5.7
*p < .05. All values are mean ± standard deviation. 8MI = body mass index; TCP02 = transcutaneous oxygen tension; A81 = ankle-brachial systolic pressure index. Six patients with nonweightbearing ulcers were excluded from analysis from the original 76 cases.
than 110 N/cm 2 for every subject with a foot ulcer, suggesting a threshold pressure below which individuals would not ulcerate. Only 31 % of diabetic subjects without a history of ulceration demonstrated abnormal peak foot pressures based on Boulton's criteria (18). However, it is not clear if a threshold pressure level exists since other reports have identified lower peak foot pressures at sites of neuropathic ulceration (17) than those identified by Boulton (15, 17, 19). For instance, diabetic subjects with peak plantar pressures above 65 Nzcm? have been shown to be at six times greater risk for ulceration than those with pressures below this value (15). Clearly, identification of an optimal peak plantar pressure cut-point to help physicians stratify diabetics by risk would be a valuable tool. Therefore, the purpose of this paper was to identify a point along the spectrum of peak plantar forefoot pressure that has an optimum combination of sensitivity and specificity to screen for neuropathic ulceration. Methods
This project was conducted as a case-control study at the Texas Diabetes Institute and The University of Texas Health Science Center Clinics at San Antonio. The Texas Diabetes Institute is a model program for multidisciplinary diabetes care and includes core participation of general internal medicine, endocrinology, ophthalmology, podiatry, diabetes nurse education, and social services. Following informed consent, all patients were enrolled sequentially from these clinics. Prior to recruitment, institutional review board approval was secured at this institution. The authors analyzed data from 76 cases and 149 controls that were diagnosed with diabetes mellitus based on World Health Organization criteria (20). Cases were defined as patients with an existing or a recently healed «4 weeks) foot ulceration (21). For the purposes of this analysis, only patients with plantars wounds were included. Six subjects with nonweightbearing ulcers were excluded. Controls were defined as subjects who had never had a foot ulceration. The authors assessed peripheral sensory neuropathy using vibration perception threshold (VPT) testing at the distal great toe using a Biothesiometer 304
THE JOURNAL OF FOOT & ANKLE SURGERY
(22,23).1 "Loss of protective sensation" was defined using the criteria described by Armstrong and co-workers (a vibration perception threshold greater than 25 V) (22). Patients with ulcers on the ankle or leg were eliminated from the study. Lower extremity peripheral vascular status was evaluated using transcutaneous oxygen tension on the dorsal aspect of the first intermetatarsal space (24), and ankle-brachial systolic blood pressure index (25). Descriptive statistics for this population are summarized in Table 1. Diabetes was stratified into type I or II, based on the algorithm described by Mogensen (26). The authors used the EMED pressure platform system to evaluate dynamic barefoot pressures on the sole of the foot pressures (27).2 The system measures pressures at a resolution of approximately 4 pixels per square centimeter over the entire surface of contact. The location and value of the largest (peak) focal pressure was recorded. This peak pressure was averaged from three recorded midgait steps on the EMED pressure platform. For selecting the optimal diagnostic cutoff points on the scale of measurement, receiver operating characteristics (ROC) curves were employed (22, 28, 29). A t-test was used for independent samples to evaluate the difference between continuous variables between groups and a chi-squared test with a 95% confidence interval was used to evaluate dichotomous variables. All values are expressed as mean ± standard deviation (30). Results
There was no significant difference in age, vascular perfusion, or body mass index between the case and control groups. Subjects with neuropathic ulceration had a significantly longer duration of diabetes than controls (41.0 ± 13.9 vs. 8.1 ± 7.4, p < .001). Males were more prevalent in the ulcer group as well (74% vs. 33%, X 2 = 33.7, p < .001). Peak plantar pressure was, as expected, significantly higher for patients with ulcers compared to controls [83.1 ± 24.7 Nzcm? (range, 10-125) vs. 62.7 ± 1
2
Biomedical Instrument Company, Newbury, OH. Novel Electronics, St. Paul, MN.
40
Conclusions
······ · No Ulcer
r>.
35
+-----+-~-----_l
-
10
Neu-opathic Ulcer
+--~~------',--..lr-
5+--.,,...:-+-- - - - ----'- -\-0-20
2 1 ~O
41-60
6 1-80
81-100 101·120
>120
Pressure (N/cm2 )
Distribution of plantar pressures by group.
FIGURE 1
21.4 N/cm 2 (range, 7.3-113), p < .001]. Figure 1 illustrates the distribution of plantar pressures in both patients with and without ulcers. The ulcer group was clearly skewed toward a higher prevalence of elevated peak plantar forefoot pressure compared with the control group, which displayed the opposite trend (control group skewness = 0.286, kurtosis = 0.482; ulcer group skewness = 0.389, kurtosis = 0.289). Results of the receiver operating characteristic analysis (ROC) are summarized in Fig. 2. As expected, cut-points delineated at relatively low plantar pressures were very sensitive for detecting risk of neuropathic ulceration, but very nonspecific (35 N/cm 2 = 98.6% sensitivity, 6.7% specificity). Conversely, cut-points made at high plantar pressures were very specific for screening for risk of ulceration, but not very sensitive (110 N/cm 2 = 15.7% sensitivity, 98.0% specificity). The optimal cut-point, as determined by a balance of sensitivity and specificity was 70 N/cm2 , which yielded a sensitivity of 70.0% and a specificity of 65.1 %.
70 N/cm'
-. -.
• •
•
..
100
•
•
'-
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-
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100
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90 80
110 ~/cm'
70 60 50
.g
40
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~
.g
30 ~ 20 10
35 N/cm 2
o 80
60
40
20
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% Sensitivity FIGURE 2 pressures.
Receiver operating characteristic curve of peak plantar
The results of this study suggest that persons with diabetes and neuropathic ulcers have significantly higher peak plantar pressures than their nonulcerated diabetic counterparts. Furthermore, this difference may ultimately offer the ability to assess for degree of risk for ulceration when used in conjunction with other contributory risk factors (31, 32). The data indicate that there may be no single point on the spectrum of peak foot pressures that can indicate with certainty when a subject will ulcerate. However, what is clearly suggested is that as peak foot pressures increase, so does the likelihood of ulceration. As other investigators have suggested, it is a combination of factors (neuropathy, foot deformity, limited joint mobility, and abnormal plantar pressures) (15) that ultimately lead to ulceration and amputation. There are three main extrinsic mechanisms of tissue breakdown in the insensitive foot (33). The common link between each of these mechanisms is mechanical stress. These mechanisms include: direct mechanical disruption of tissue (e.g., a foreign body puncturing the skin), prolonged pressure over a small area leading to local ischemia and tissue breakdown (e.g., a bunion deformity precipitating an ulcer on the medial margin of the foot), and repetitive moderate forces leading to inflammation and enzymatic autolysis (e.g., ambulation on an unprotected foot leading to skin breakdown beneath a prominent metatarsal head). This third mechanism is the most common etiology of the plantar diabetic foot ulcer (34). This should come as no surprise, since cyclic loading is the most widely accepted precipitating factor in failure of materials. This phenomenon, termed fatigue, stipulates that the majority of catastrophic failures experienced by a material are due to many cycles of loading at a stress level that is lower than the strength (or maximum stress) of the material. The second and third mechanisms of injury described above are precipitated by two main factors, foot deformity and limited joint mobility, which in tum lead to increased plantar foot pressures. Plantar foot pressures, when elevated, theoretically require less repetitive stress to initiate soft-tissue breakdown. Again, this statement agrees with the concept of fatigue failure, which predicts that the higher the stress level, the smaller the number of cycles that will be required by a material to fail. It, therefore, should come as no surprise that in this study foot ulcers were associated with a higher prevalence of elevated foot pressures. A limitation of this study is the evaluation of total compressive stress as the sole determining mechanical factor. Although this is currently the accepted modality, it should be borne in mind that shear stress and its concomitant strain may be at least equally relevant in determining soft tissues' propensity for breakdown at the VOLUME 37, NUMBER 4, JULY/AUGUST 1998
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plantar aspect of the foot. Unfortunately, at this time there is not a well accepted, validated devise to measure shear stress and strain in vivo, and the authors were therefore not able to evaluate this variable. Reducing foot pressures on the sole of the foot with therapeutic footwear and prosthetics is pivotal to prevent the development of ulcers in high-risk patients and to heal ulcers once they develop (35). Much of the recent literature in wound healing has focused on expensive, high-tech growth factors and bioengineered tissue with less than sterling results (36). None of these studies seem to have adequately off-loaded the foot, and therefore healing rates were far less than in studies that used prosthetics that have been shown to possess superior pressure reduction capabilities (17, 37 -43). This continues to be an area that needs to be scientifically evaluated in greater detail. Only until we identify and accommodate for high plantar pressure through appropriate shoe gear and prostheses for all insensate diabetic patients (35) will we be able to reduce the unconscionably high number of preventable lower extremity amputations throughout the industrialized and developing world. References 1. Armstrong, D. G., Lavery, L. A., van Houtum, W. H., Harkless, L. B. Seasonal variations in lower extremity amputation. J Foot Ankle Surg. 36:146-150, 1997. 2. Lavery, L. A., Ashry, H. R., van Houtum, W., Pugh, J. A., Harkless, L. B., Basu, S. Variation in the incidence and proportion of diabetes-related amputations in minorities. Diabetes Care 19:48 - 52, 1996. 3. van Houtum, W. H., Lavery, L. A., Harkless, L. B. The impact of diabetes-related lower extremity amputations in the Netherlands. Diabetes and Its Complications 10:325-330, 1996. 4. Armstrong, D. G., Lavery, L. A., Harkless, L. B., van Houtum, W. H. Amputation and reamputation of the diabetic foot. JAPMA 87:255-259, 1997. 5. Murdoch, D. P., Armstrong, D. G., Dacus, J. B., Laughlin, T. J., Morgan, C. B., Lavery, L. A. The natural history of great toe amputations. J Foot Ankle Surg 36:204-208, 1997. 6. Goldner, M. G. The fate of the second leg in the diabetic amputee. Diabetes 9:100-103,1960. 7. Whitehouse, F. W., Jurgenson, c., Black, M. A. The later life of the diabetic amputee. Diabetes 17:520-521, 1968. 8. Lavery, L. A., van Houtum, W. H., Harkless, L. B. In-hospital mortality and disposition of diabetic amputees in the Netherlands. Diabetic Med. 13:192-197, 1996. 9. van Houtum, W. H., Lavery, L. A. Outcomes associated with diabetes-related amputations in the Netherlands and in the State of California, USA. J. Intern. Med. 240:227-231, 1996. 10. Lavery, L. A., van Houtum, W. H., Armstrong, D. G. Institutionalization following diabetes-related lower extremity amputation. Am. J. Med. 103:383-388, 1997. 11. Muecke, L., Shekar, S., Dwyer, D., Israel, E., Flynn, P. G. Functional screening of lower-limb amputees: a role in predicting rehabilitation outcome? Arch. Phys. Med. Rehabi1. 73:851-858, 1992. 12. Edmonds, M. E., Blundell, M. P., Moms, M. E., Thomas, E. M., Cotton, L. T., Watkins, P. J. Improved survival of the diabetic foot: the role of a specialized foot clinic. Q. J. Med. 60:763-771, 1986.
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13. Edmonds, M. E. Experience in a multidisciplinary diabetic foot clinic. In: Connor H Boulton AJM Ward JD, ed. The Foot in Diabetes, pp. 121-131, edited by H. Connor, A. J. M. Boulton, J. D. Ward, Wiley, Chichester, 1987. 14. Runyan, J. W. The Memphis chronic disease program: Comparisons in outcome and the nurses extended role. JAMA 231 :264- 267, 1975. 15. Lavery, L. A., Armstrong, D. G., Vela, S. A., Quebedeaux, T. L., Fleischli, J. G. Practical criteria for screening patients at high risk for diabetic foot ulceration. Arch. Intern. Med. 158:158-162, 1998. 16. Pecoraro, R. E., Reiber, G. E., Burgess, E. M. Pathways to diabetic limb amputation: Basis for prevention. Diabetes Care 13:513-521, 1990. 17. Armstrong, D. G., Lavery, L. A., Bushman, T. R. Peak foot pressures influence healing time of diabetic ulcers treated with total contact casting. J. Rehabi1. Res. Dev. 35:1-5,1998. 18. Boulton, A. J. M., Connor, H., Hardisty, C. A., et a1. Dynamic foot pressure and other studies as diagnostic and management aids in diabetic neuropathy. Diabetes Care 6:26, 1983. 19. Boulton, A. J. M., Hardisty, C. A., Belts, R. P., Franks, C. 1., Worth, R. C., Ward, J. D., Duckworth, T. Dynamic foot pressure and other studies as diagnostic and management aids in diabetic neuropathy. Diabetes Care 6:26-33, 1983. 20. World Health Organization. Second Report on Diabetes Mellitus, World Health Organization, Geneva, 1980. 21. Armstrong, D. G., Lavery, L. A., Harkless, L. B. Validation of a diabetic wound classification system: the independent contribution of depth, infection, and vascular disease to the risk of amputation. Diabetes Care 21:855-859, 1998. 22. Armstrong, D. G., Lavery, L. A., Vela, S. A., Quebedeaux, T. L., Fleischli, J. G. Choosing a practical screening instrument to identify patients at risk for diabetic foot ulceration. Arch. Intern. Med. 158:289-292, 1998. 23. Young, M. J., Breddy, J. L., Veves, A., Boulton, A. J. M. The prediction of diabetic neuropathic foot ulceration using vibration perception thresholds. Diabetes Care 16:557 - 560, 1994. 24. McNeely, M. J., Boyko, E. J., Ahroni, J. E., Stensel, V. L., Reiber, G. E., Smith, D. G., Pecoraro, R. E. The independent contributions of diabetic neuropathy and vasculopathy in foot ulceration. Diabetes Care 18:216-219, 1995. 25. Beach, K. W., Strandness, D. E. Arteriosclerosis obliterans and associated risk factors in insulin-dependent and non-insulin dependent diabetes. Diabetes 29:882-888, 1980. 26. Mogensen, C. E. Renoproductive role of ACE inhibitors in diabetic nephropathy. Br. Heart J. 72 (Suppl):38-45, 1994. 27. Graf, P. M. The EMed system of foot pressure analysis. Clin. Pod. Med. Surg. 10:445-454, 1993. 28. Bortheiry, A. L., Malerbi, D. A., Franco, L. J. The ROC curve in the evaluation of fasting capillary blood glucose as a screening test for diabetes and IGT. Diabetes Care 11:1269-1272, 1994. 29. Tsuji, L., Nakamoto, K., Hasegawa, T., Gohdes, D. M., Inawashiro, H., Fukao, A. Receiver operating characteristic analysis on fasting plasma glucose, HbAlc, and fructosamine on diabetes screening. Diabetes Care 14:1075 -1077, 1992. 30. Kirkwood, B. R. Essentials of Medical Statistics, Blackwell, Oxford, 1988. 31. Armstrong, D. G., Lavery, L. A., Harkless, L. B. Treatment-based classification system for assessment and care of diabetic feet. J. Am. Podiatr. Med. Assoc. 86:311-316,1996. 32. Armstrong, D. G., Lavery, L. A. Elevated peak plantar pressure in patients who have Charcot arthropathy. J. Bone Joint Surg. 80A:365-369, 1998. 33. Hall, O. c., Brand, P. W. The etiology of the neuropathic plantar ulcer. J. Am. Podiatry Assoc. 69:173-177,1979.
34. Tredwell, J. Pathophysiology of tissue breakdown in the diabetic foot. In Medical and Surgical Management of the Diabetic Foot, pp. 97 - 112, edited by S. J. Kominsky, Mosby-Year Book, St. Louis, MO, 1994. 35. Lavery, L. A., Vela, S. A., Fleischli, J. G., Armstrong, D. G., Lavery, D. C. Reducing plantar pressure in the neuropathic foot: a comparison of footwear. Diabetes Care 20: 1706 - 1710, 1997. 36. Gentzkow, G. D., Iwasaki, S. D., Hershon, K. S. Use of dermagraft, a cultured human dermis, to treat diabetic foot ulcers. Diabetes Care 19:350-354, 1996. 37. Walker, S. C, Helm, P. A., Pulliam, G. Total contact casting and chronic diabetic neuropathic foot ulcerations: Healing rates by wound location. Arch. Phys. Med. Rehabil. 68:217-221,1987. 38. Walker, S. C, Helm, P. A., Pulliam, G. Chronic diabetic neuropathic foot ulcerations and total contact casting: Healing effectiveness and outcome probability (abstr.). Arch. Phys. Med. Rehabil. 66:574, 1985.
39. Lavery, L. A., Armstrong, D. G., Walker, S. C Healing rates of diabetic foot ulcers associated with midfoot fracture due to Charcot's arthropathy. Diabetic Med. 14:46-49, 1997. 40. Lavery, L. A., Vela, S. A., Lavery, D. C., Quebedaux, T. L. Reducing dynamic foot pressures in high risk diabetics with foot ulcerations: a comparison of treatments. Diabetes Care 19:818-821, 1996. 41. Mueller, M. J., Diamond, J. E., Sinacore, D. R., Blair, V. P., Drury, D., Rose, S. J. Total contact casting in treatment of diabetic plantar ulcers. Diabetes Care 12:384-387, 1989. 42. Sinacore, D. R., Mueller, M. J., Diamond, J. E. Diabetic plantar ulcers treated by total contact casting. Phys. Ther. 67: 1543-1547, 1987. 43. Chantelau, E., Breuer, D., Leisch, A. C, Tanudjada, T., Reuter, M. Outpatient treatment of unilateral diabetic foot ulcers with 'half shoes'. Diabetic Med. 10:267-270, 1993.
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