Guidelines for the treatment of diabetic ulcers

Abstract

Diabetic foot ulcers are a significant health care problem. Complications of foot ulcers are a leading cause of hospitalization and amputation in patients with diabetes mellitus. In response to a request from the Wound Healing Society, a panel of advisers, including physicians from academia and private practice, nurses, a podiatrist, a pedorthist, and a representative from industry, was selected to develop guidelines for the treatment of diabetic ulcers of the lower extremity. The approach used to develop guidelines was similar to that used by the Venous Ulcer Panel, also convened at the request of the Wound Healing Society. Those guidelines were presented on October 3, 2005, at a conference at the National Institutes of Health (NIH). Previous guidelines, meta-analyses, PubMed, MEDLINE, EMBASE, The Cochrane Database of Systematic Reviews, recent reviews of diabetic ulcer treatment, and the Medicare/CMS consensus of usual treatment of chronic wounds were reviewed for evidence. Guidelines were formulated, the underlying principle(s) enumerated, and evidence references listed and coded. The code abbreviations for the evidence citations were as follows: There was a major difference between our approach to evidence citations and past approaches to evidence-based guidelines. Most past approaches relied only on publications regarding clinical human studies. Laboratory or animal studies were not cited. We have used well-controlled animal studies that present proof of principle, especially when a clinical series corroborated the laboratory results. Because of this variation, a different system was used to grade the weight of evidence supporting a given guideline. The strength of evidence supporting a guideline is listed as Level I, Level II, or Level III. The guideline levels are: Level I: Meta-analysis of multiple RCTs or at least two RCTs supporting the intervention of the guideline. Another route would be multiple laboratory or animal experiments with at least two clinical series supporting the laboratory results. Level II: Less than Level I, but at least one RCT and at least two significant clinical series or expert opinion papers with literature reviews supporting the intervention. Experimental evidence that is quite convincing, but not yet supported by adequate human experience. Level III: Suggestive data of proof of principle, but lacking sufficient data such as meta-analysis, RCT, or multiple clinical series. Note: The suggestion in the guideline can be positive or negative at the proposed level (e.g., meta-analysis and two RCTs stating intervention is not of use in treating diabetic ulcers). Guidelines have been formulated in eight categories for the treatment of diabetic ulcers of the lower extremities. The categories are: Diagnosis Offloading Infection control Wound bed preparation Dressings Surgery Adjuvant agents (topical, device, systemic) Prevention of recurrence Each of the separate guidelines is undergoing a Delphi consensus among the panel members. Not all panel members thought they had sufficient expertise to critique all of the separate sections of the guidelines. However, each set of guidelines was critically evaluated by at least ten panel members. Preamble: Ulcers of the lower extremity may be caused by a variety of conditions, including neuropathy, ischemia, venous hypertension, and pressure. Patients with diabetes develop wounds secondary to neuropathy with or without biomechanical abnormalities, peripheral vascular disease with ischemia, or both. There are 20 million people in the United States with diabetes, of whom 10–15% are at risk for ulceration. It is imperative that the etiology be established to provide for proper therapy. Guideline #1.1: Clinically significant arterial disease should be ruled out by establishing that pedal pulses are clearly palpable or that the ankle : brachial index (ABI) is >0.9. An ABI >1.3 suggests noncompressible arteries. In elderly patients or patients with an ABI >1.2, a normal Doppler-derived waveform, a toe : brachial index of >0.7, or a transcutaneous oxygen pressure of >40 mmHg may help to suggest an adequate arterial flow. Color duplex ultrasound scanning provides anatomic and physiologic data confirming an ischemic etiology for the leg wound. (Level I) Principle: Diabetic ulcers can result from arterial insufficiency or neuropathy. Although clinical history and physical examination can be very suggestive of an ischemic etiology of the lower extremity diabetic ulcers, a definitive diagnosis must be established. When significant arterial disease is present, successful treatment requires that arterial insufficiency be addressed. Evidence: Sahli D, Eliasson B, Svensson M, Blohme G, Eliasson M, Samuelsson P, Ojbrandt K, Eriksson J. Assessment of toe blood pressure is an effective screening method to identify diabetes patients with lower extremity arterial disease. Angiology 2004; 55: 641–51. [CLIN S] Teodorescu V, Chen C, Morrissey N, Faries P, Marin M, Hollier L. Detailed protocol of ischemia and the use of noninvasive vascular laboratory testing in diabetic foot ulcers. Am J Surg 2004; 187 (5A): 75S–80. [LIT REV] Hirsch A, Criqui M, Treat-Jacobson D, Regensteiner J, Creager M, Olin J, Krook S, Hunninghake D, Comerota A, Walsh M, McDermott M, Hiatt W. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA 2001; 286: 1317–24. [CLIN S] Ascher E, Hingorani A, Markevich N, Yorkovich W, Schutzer R, Hou A, Jacob T, Nahata S, Kallakuri S. Role of duplex arteriography as the sole preoperative imaging modality prior to lower extremity revascularization surgery in diabetic and renal patients. Ann Vasc Surg 2004; 18: 433–439. [CLIN S] Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WRC, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM Jr, White CJ, White J, White RA. ACC/AHA guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society for Vascular Medicine and Biology, and the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to develop guidelines for the management of patients with peripheral arterial disease). American College of Cardiology Web site. Available at: http://www.acc.org/clinical/guidelines/pad/index.pdf. [STAT] Padberg FT, Back TL, Thompson PN, Hobson RW. Transcutaneous oxygen (TcPO2) estimates probability of in the ischemic extremity. J Surg [CLIN S] Guideline The of significant neuropathy can be by testing with a (Level Principle: to foot with pressure on the especially the of in of pressure. neuropathy may the of Evidence: N, D, foot ulcers in patients with JAMA [LIT REV] N, K, S, T, K, R, M, of examination for diabetic peripheral neuropathy J Complications [CLIN S] K, S. of a for of foot in patients with J Surg 2004; [CLIN S] A, P, V, V, J. of patients at risk for diabetic a of noninvasive testing with at diabetes J Complications 2001; [CLIN S] J, J. The use of the and for foot and amputation in with J [LIT REV] D, C, J, to identify people at risk for diabetic foot a [CLIN S] M, D, D, E, J, examination for the of in the of diabetic patients. for J [CLIN S] S, D, A, E, M, a effective and screening for diabetic patients at risk of foot ulceration. [CLIN S] J, R, P, of pressure in diabetic peripheral neuropathy. J [CLIN S] TL, for screening patients at risk for diabetic foot ulceration. [CLIN S] J, of foot pressure as of a diabetes disease management [CLIN S] Preamble: Diabetic may result from an in pressure on the diabetic foot of foot and neuropathy. Offloading the of pressure been the to Guideline should be in at risk for amputation arterial significant neuropathy, ulcer foot evidence of (Level Principle: The of in diabetic patients at risk for can be by Evidence: The for for diabetic patients. [CLIN S] M, M, E, of American and Society. Guidelines for diabetic foot by the of the American and Society. [LIT REV] C, K, S, C, J. of on foot in patients with a JAMA C, S, of diabetic in 2004; [LIT REV] E, T, effective is in diabetic clinical [CLIN S] E, An of diabetic to [CLIN S] E, G, A, A, P, in the of diabetic foot ulcers. 18: Guideline of diabetic and and (Level I) Principle: pressure on the diabetic is to Evidence: I, A, B, D, J, M, of two in management of diabetic foot ulcers. D, C, A, L. the diabetic foot clinical 2001; R, R, The of on 2004; S] G, A, S, in the treatment of diabetic and [CLIN S] A, P, G, M, V, S. of the of the foot of pressure [CLIN S] J, P, in an 2004; [LIT REV] MA, of ulcer in patients with diabetes mellitus. Wound S] P, S, in diabetic patients with foot [CLIN S] Preamble: Infection when the : is in of the Infection in the and of diabetic ulcers. Guideline all or by or (Level of is in Wound Principle: is with the to and as a for Evidence: in of Wound in M, N, The of chronic a Health [STAT] D, D, M, and the Diabetic Ulcer of and treatment on the of diabetic foot ulcers. J Am Surg of and [LIT REV] Wound bed preparation and the of a for multiple of [LIT REV] W. of Ann Surg index and with of diabetic foot ulcers. Wound G, G, R, Taylor for chronic venous leg ulcers. J [LIT REV] Guideline is in a or from the is not two of and of the and level of in a diabetic ulcer by or by a (Level Principle: levels of of or a level of the and have been to and of diabetic ulcers. should be to and Evidence: Wound caused by Surg [LIT REV] Wound a of caused by an of Surg Am [LIT REV] M, in diabetic patients with ulcers of 2001; for diabetic foot ulcers. [LIT REV] of and Surg Am [LIT REV] on a Role in the of the The and a method for the of on J The a a Am J Surg [STAT] P, I, K, C, C, K, the of chronic wounds in J [CLIN S] in diabetic the of 20 [LIT REV] The of in chronic leg ulcers. Ann Surg [CLIN S] of chronic leg ulcers. Guideline ulcers with of or level of adequate the level with a in the use of the to to the or of to the (Level I) Principle: not levels in can be Evidence: Wound a of caused by an of Surg Am [LIT REV] I, C, P, C, The of in leg ulcer by a a of Am J Surg The of in chronic leg ulcers. Ann Surg [CLIN S] White R, Wound and the of J 2001; [LIT REV] of chronic leg ulcers. Guideline diabetic foot not to the are (Level Principle: have been in to be in treating diabetic foot Although the are to and are are in Evidence: on and the Diabetic a report from the consensus on and treating the diabetic 2004; 20 [STAT] S, N, M, Systematic reviews of care agents for chronic diabetic foot ulceration. Health [STAT] and of of diabetic foot [LIT REV] A, D, for diabetic foot Guideline and of the and to or the ulcer should be with (Level Principle: the of and the normal of the and to by and Evidence: E, with to the of the an J [LIT REV] K, and of the J 2001; [LIT REV] of and [LIT REV] W. of the J [LIT REV] S, T, of in patients with and therapy. Guideline is the with a and (Level Principle: underlying a diabetic ulcer is of the a definitive but can be in establishing a diagnosis with a of and Evidence: K, E, to in pedal ulcers. clinical of underlying in diabetic patients. JAMA [CLIN S] M, on the diagnosis and management of Surg [LIT REV] D, K, J, A, Systematic and meta-analysis of for and 2001; [STAT] The use of of Surg [CLIN S] Guideline is by of the by of However, when this is not underlying a diabetic ulcer can be with therapy. (Level Principle: underlying a diabetic is by of the When been a of is the is not a least is Evidence: D, K, J, Systematic and meta-analysis of for and 2001; [STAT] and of of diabetic foot [LIT REV] treatment of have from of clinical J [LIT REV] J. of and in the management of J Surg M, on the diagnosis and management of Surg [LIT REV] Guideline the level of to of with in the ulcer by or (Level Principle: with than of be as the of that is Evidence: of Surg [LIT REV] E, The of on the of in Ann Surg and Surg 18: Murphy The of on and J Surg of and Surg Am [LIT REV] M, in diabetic patients with ulcers of 2001; of and are in Infection Dressings and Adjuvant and Preamble: Wound bed preparation is as the management of the to or the of The of bed preparation is to the and of a chronic to that of an wound. The of bed preparation have been V, Wound bed a approach to Wound D, the and Guideline of the as a is to and of such and and and (Level I) Principle: including a help in and of The of a major or disease and such as and with by in and such as or can all and may or agents can Patients undergoing major surgery have a as chronic is with and risk of Evidence: D, R, G, and guidelines for of wounds and of [STAT] Healing of and in [LIT REV] R, S. M, of in of the T, major J Surg [CLIN S] A, of and on and of and Surgery 2004; chronic a on and for therapy. Am J Surg 2004; 187 (5A): [LIT REV] Principle: must be adequate to provide sufficient to the of The level recent and are in patients are the Although diabetic ulcer patients are and not at the of is an is Evidence: I, M, V, N, J, G, J. of the of in critically II: a in the management of J 2004; [LIT REV] and weight the of intervention in [LIT REV] Principle: in an that is to the be is and that such as or oxygen by peripheral must be or Evidence: N, W, management of and oxygen in patients. Ann Surg [CLIN S] B, as an of the of oxygen and on in Surg Wound and and can Surg Am [LIT REV] K, J, and in to in patients. Ann Surg Surg P, W, J, K, P, J, R, K, J. Wound oxygen the risk of in patients. Surg [CLIN S] in and J Surg 2004; [LIT REV] 2004; [LIT REV] R, E, A, oxygen to the of J Guideline is to the and of and is to the and of the bed for The health care can from a of including or than one method may be is Level Principle: and can all The method of may on the of the the of the health the of the and Evidence: D, and the Diabetic Ulcer of on the of diabetic foot ulcers. J Am Surg index and with of diabetic foot ulcers. Wound for A, of and for pressure ulcer Am J Surg 2004; 187 [LIT REV] the Wound 2004; [LIT REV] J. and Wound [LIT REV] D, K, D, D, the and [LIT REV] J, of of a Wound M, N, The of chronic a Health [STAT] The of on and in J Surg Wound bed preparation and the of a for multiple of the [LIT REV] in the treatment of and ulcers. J Am [CLIN S] The and of two J S] A, E, M, C, approach management for diabetic foot a Diabetic JL, J, Diabetic foot of two and Wound Guideline should be and at each a should be with a of (Level Principle: and the to or is should only be used the is Experimental data suggest that a may be as may by pressure. Evidence: Wound D, D, Wound for Health [LIT REV] S, clinical with in vascular care. J Wound [CLIN S] a Ann of Ann Surg Guideline There should be an and of and of the and to bed The of should be evaluated to treatment is (Level Principle: of bed preparation are the ulcer is not at the for bed preparation to be The the of the the is to an ulcer is or of and to be Evidence: and guidelines for of wounds and of [STAT] index and with of diabetic foot ulcers. Wound Wound Healing a Wound Wound as of of Surg [STAT] Guideline Patients to a in ulcer by or of should be and should be (Level Principle: in of diabetic foot ulcers of treatment is a of of and of Evidence: P, P, A, in of diabetic foot ulcers a is a of in a [CLIN S] Wound as of of Surg [CLIN S] Wound and approaches to Surg 2001; [LIT REV] L. leg and of Ulcer J [CLIN S] Guideline control (Level Principle: Wound is to be in the of diabetes levels also the of Evidence: A, of diabetic foot ulcers with a blood [CLIN S] M, M, of control on in diabetic J Wound [CLIN S] in to J Am [CLIN S] at diabetes and Am J Surg N, I, of diabetic on in diabetic J, S, in J 2004; The of blood control in the with diabetes mellitus. J of in diabetic requires preoperative blood J Surg N, G, M, D, T, on for diabetes 2001; Wound and diabetes mellitus. Surg [LIT REV] C, control and the risk of in a of with [CLIN S] Preamble: There is a of for treatment of diabetic ulcers. bed with Guidelines are to help the regarding the and use of care Most be used in with and of the Guideline a that a (Level Principle: and of wounds by also Evidence: of and on the of a wound. K, Eriksson E, P, Healing of wounds in a J Surg T, B, J, Eriksson of wounds in a Surg J, S, N, T, S, K, R, J, D, Eriksson Surg [CLIN S] Guideline clinical to a (Level Principle: are not are as effective as of in of Evidence: The of two on J Surg P, M, of J Surg J, S, S. Healing of J Wound M, N, M, T, Systematic reviews of care and agents used in the of chronic Health [STAT] of a in the management of diabetic foot ulcers. Wound [CLIN S] Guideline a that the and the (Level I) Principle: and with can the and Evidence: B, of by chronic Wound S, N, J, Murphy G, of the and chronic the of and Wound Wound from human pressure ulcers levels and to J J, S, S. Healing of J Wound R, P, V, S, G, G, J, S, J, J. and of in the treatment of diabetic foot Guideline a that in and and not cause (Level Principle: Wound and can all the of Evidence: D, D, from Am J [CLIN S] Guideline a that is (Level I) Principle: Because of are as the least However, when is to health care of and as as the of the Evidence: P, K, C, of leg ulcer treatment in primary care. of and treatment in a J Health K, P, B, and of and in the management of patients with chronic leg 2001; care a clinical Wound [LIT REV] Guideline use agents (topical, device, systemic) a and ulcer and when is a of in response to of are in Adjuvant Level Principle: and may and in selected patients or are quite and are in in the Adjuvant Evidence: references are in the Adjuvant P, for treatment of diabetic foot ulcers. Am J Surg 2004; 187 (5A): [LIT REV] Preamble: The of and are not successful in all diabetic ulcers. the multiple have been to diabetic ulcers with of clinical are but data are supporting surgery in selected patients. Guideline may of diabetic (Level Principle: the pressure on ulcers in patients with and may be of in diabetic foot ulcers. Evidence: M, D, M, M, J. of on ulcers. clinical J Surg G, C, the for the treatment of diabetic ulceration. Surg Am [LIT REV] S, L. of the in diabetic patients are at risk for of the J Surg [CLIN S] with of the ankle in diabetic the of and [CLIN S] for the treatment of ulcers a in pressure with in than ankle J 2004; [CLIN S] Guideline Patients with ischemia should be for a revascularization Principle: In patients with arterial in blood is with an in and Evidence: P, on Wound Healing and for with Diabetic 2004; [LIT REV] T, Vascular and of the diabetic Surg [LIT REV] K, and clinical of arterial in diabetic and of J Vasc Surg [CLIN S] E, M, M, use of peripheral in the treatment of diabetic foot clinical of a of diabetic J [CLIN S] D, extremity revascularization in Surg [CLIN S] A, arterial for foot ischemia in patients with diabetes mellitus. J Vasc Surg [CLIN S] Preamble: agents have been to be used as to and in the treatment of diabetic ulcers. agents can be agents to be to the at ulcer and to the of agents have evidence to guidelines regarding Guideline is effective in treating diabetic foot ulcers. (Level I) Principle: are in Evidence: D, Diabetic Ulcer of human for the treatment of lower extremity diabetic ulcers. J Vasc Surg J, J, and of a of human in patients with chronic diabetic a in patients with lower extremity ulcers. J, and of human in patients with lower extremity diabetic a of studies. Wound [STAT] J, V, D, the of clinical with the that is an effective to the treatment of diabetic foot ulcers. J [STAT] Guideline not yet have data on to of for treatment of diabetic ulcers, suggest (Level I) Principle: are in Evidence: in chronic diabetic foot ulcers. G, D, M, T, response of in diabetic S, J, D, of in of ulcers. Surgery D, K, V, and treatment of chronic ulcers Surg D, K, V, S, E, of in ulcers Surg JL, C, of on the of chronic diabetic ulcer of the 18: of on in diabetic foot ulcers. J of ulcers in patients with diabetes by treatment with Wound S, S, in foot ulcers. Diabetic [CLIN S] G, M, G, P, P, of as for diabetic foot 2001; A, M, N, J, of in diabetic foot W, G, C, of diabetic foot ulcers. Guideline pressure may be of in treating diabetic (Level I) Principle: treatment may by and the of the and should be when are not Evidence: M, K, G, J, of for diabetic foot Ann Vasc Surg S, C, J, M, J, L. in the of diabetic foot D, L. Diabetic negative pressure diabetic foot a M, T, S, R, D, L. with the negative pressure in the treatment of diabetic and S] D, C, A, R, R, J. Guidelines regarding negative in the diabetic 2004; [LIT REV] D, L. negative pressure for treating chronic Cochrane Database 2001; [STAT] Guideline may be of in diabetic foot ulcers. (Level I) Principle: in diabetic foot ulcers by of and that the Evidence: P, Diabetic Ulcer the and of in the of chronic diabetic foot of a A, V, Diabetic Ulcer a human is effective in the management of diabetic foot a clinical 2001; Healing of chronic foot ulcers in diabetic patients with a human J Surg J, P, K, The of treatment of diabetic foot ulcers. [STAT] J, T, Hollier L. Healing of diabetic foot ulcers and pressure ulcers with human a in Surg [CLIN S] a use in the treatment of venous leg ulcers and diabetic foot ulcers. [LIT REV] a human for the treatment of chronic diabetic foot ulcers. 2004; [LIT REV] Guideline may be of in diabetic foot ulcers. (Level I) Principle: of to wounds may and Evidence: for a of evidence from in animal and clinical J [LIT REV] P, C, M, K, D, M, of on chronic leg ulcer and T, Eriksson S, of diabetic ulcers. Ann Surg of on the of wounds in diabetic Wound 2001; as an to diabetic foot a clinical 2001; Guideline oxygen may be of in the amputation in patients with ischemic diabetic foot ulcers. (Level I) Principle: oxygen may the of oxygen to a in diabetic patients and Evidence: C, S, E, D, J. oxygen for treating a of the Surg [LIT REV] A, G, G, B, A, P, E, The of oxygen in ischemic diabetic lower extremity a J Vasc Surg A, G, G, B, Role of oxygen in a J Surg 2001; E, A, P, A, G, M, P, oxygen in treatment of ischemic diabetic foot T, Chen S, The vascular of oxygen in treatment of diabetic 2001; [CLIN S] C, oxygen of chronic leg a Surg P, C, R, D, M, the of chronic diabetic foot a P, M, I, S. oxygen for chronic Cochrane Database [STAT] oxygen lower extremity and the diabetic [LIT REV] Preamble: Diabetic ulcers of the lower extremity are a chronic problem. are must be for ulcers. Guideline Patients with diabetic ulcers should use to (Level Principle: Most not the underlying pressure on the is Evidence: M, G, D, C, S, of diabetic in 2004; [LIT REV] for people with 2004; 20 [LIT REV] and the diabetic clinical and Am J Surg 2004; 187 (5A): [LIT REV] management of the diabetic 2001; [LIT REV] R, R, G, K, W, of on foot as by in diabetic a 2001; 18: E, G, A, A, P, in the of diabetic foot ulcers. 18: S, V, Taylor L. of to in people with [CLIN S] A, in treatment of diabetic ulcers. clinical [CLIN S] Guideline foot care and of the the recurrence of diabetic ulceration. (Level Principle: foot care including proper and proper in diabetic Evidence: M, M, E, of American and Society. Guidelines for diabetic foot by the of the American and Society. [LIT REV] W, P, on Wound Healing and for with Diabetic Wound and for people with diabetic foot ulcers. 2004; 20 [LIT REV] The diabetic [LIT REV] foot in patients with diabetes mellitus. J [STAT] of foot in patients with [STAT] K, and lower extremity risk and in [CLIN S] was supported by the Wound Healing a to the Wound Healing Society.