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Risk factors for impaired wound healing and wound complications

David G Armstrong, DPM, MD, PhD
Andrew J Meyr, DPM
Section Editors
Russell S Berman, MD
John F Eidt, MD
Joseph L Mills, Sr, MD
Deputy Editor
Kathryn A Collins, MD, PhD, FACS


Acute wounds in normal, healthy individuals heal through an orderly sequence of physiological events. Some individuals have one or more factors that contribute to impaired wound healing, which can lead to chronic nonhealing wounds and ulcers or can complicate the surgical course.

The risk factors associated with impaired wound healing due to patient factors, underlying disease, and disease treatments are reviewed here. Wound mechanisms, normal phases of wound healing, and wound classification as well as the clinical evaluation and management of wounds are discussed elsewhere. (See "Basic principles of wound healing" and "Clinical assessment of wounds" and "Basic principles of wound management" and "Overview of treatment of chronic wounds".)


Impaired wound healing — A wound is a disruption of the normal structure and function of the skin and underlying soft tissue [1]. Acute wounds in normal, healthy individuals heal through an orderly sequence of physiological events. (See "Basic principles of wound healing".)

The overlapping intricacy of the wound healing pathway serves to prevent a single primary factor from disrupting the process. As examples, local tissue ischemia and neuropathy can impair chemotaxis during the hemostasis and inflammatory stages, tissue necrosis and infection alter the balance of inflammation and compete for oxygen, and uncontrolled periwound edema and wound instability disrupt myofibroblast activity, collagen deposition, and cross-linking. Impaired wound healing often occurs in the setting of multiple, smaller contributing issues to stall the healing process; however, infection or ischemia alone can impair wound healing.

When the healing process is stalled, a chronic wound may develop, and this is more likely to occur in patients with underlying medical disorders. Chronic ulceration commonly affects the lower extremities with a prevalence that ranges between 0.18 and 1.3 percent in the adult population [2-5]. The most common nonhealing wounds affecting the lower extremities are associated with chronic venous insufficiency, peripheral artery disease, and diabetes mellitus [1,2,6-8].

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Literature review current through: Nov 2017. | This topic last updated: Jun 28, 2017.
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  1. Orr JW, Taylor PT. Wound healing. In: Complications in gynecological surgery: Prevention, recognition, and management, JB Lippincott, Philadelphia p.167.
  2. Lipscomb, GH, Ling, FG. Wound Healing, Suture Material, and Surgical Instrumentation. In: TeLinde's Operative Gynecology, 9th edition, Rock, JA, Jones, HA, III (Eds), 2003. p.233.
  3. Diegelmann RF, Evans MC. Wound healing: an overview of acute, fibrotic and delayed healing. Front Biosci 2004; 9:283.
  4. Leibovich SJ, Ross R. The role of the macrophage in wound repair. A study with hydrocortisone and antimacrophage serum. Am J Pathol 1975; 78:71.
  5. Mor-Vaknin N, Punturieri A, Sitwala K, Markovitz DM. Vimentin is secreted by activated macrophages. Nat Cell Biol 2003; 5:59.
  6. Armstrong DG, Lavery LA, Harkless LB. Validation of a diabetic wound classification system. The contribution of depth, infection, and ischemia to risk of amputation. Diabetes Care 1998; 21:855.
  7. Morbach S, Furchert H, Gröblinghoff U, et al. Long-term prognosis of diabetic foot patients and their limbs: amputation and death over the course of a decade. Diabetes Care 2012; 35:2021.
  8. Mills JL Sr, Conte MS, Armstrong DG, et al. The Society for Vascular Surgery Lower Extremity Threatened Limb Classification System: risk stratification based on wound, ischemia, and foot infection (WIfI). J Vasc Surg 2014; 59:220.
  9. Freedman G, Cean C, Duron V, et al. Pathogenesis and treatment of pain in patients with chronic wounds. Surg Technol Int 2003; 11:168.
  10. Bowler PG, Duerden BI, Armstrong DG. Wound microbiology and associated approaches to wound management. Clin Microbiol Rev 2001; 14:244.
  11. Lipsky BA, Berendt AR, Cornia PB, et al. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis 2012; 54:e132.
  12. Horan TC, Gaynes RP, Martone WJ, et al. CDC definitions of nosocomial surgical site infections, 1992: a modification of CDC definitions of surgical wound infections. Infect Control Hosp Epidemiol 1992; 13:606.
  13. Consensus paper on the surveillance of surgical wound infections. The Society for Hospital Epidemiology of America; The Association for Practitioners in Infection Control; The Centers for Disease Control; The Surgical Infection Society. Infect Control Hosp Epidemiol 1992; 13:599.
  14. Lewis SS, Moehring RW, Chen LF, et al. Assessing the relative burden of hospital-acquired infections in a network of community hospitals. Infect Control Hosp Epidemiol 2013; 34:1229.
  15. Boyce JM, Potter-Bynoe G, Dziobek L. Hospital reimbursement patterns among patients with surgical wound infections following open heart surgery. Infect Control Hosp Epidemiol 1990; 11:89.
  16. Poulsen KB, Bremmelgaard A, Sørensen AI, et al. Estimated costs of postoperative wound infections. A case-control study of marginal hospital and social security costs. Epidemiol Infect 1994; 113:283.
  17. Vegas AA, Jodra VM, García ML. Nosocomial infection in surgery wards: a controlled study of increased duration of hospital stays and direct cost of hospitalization. Eur J Epidemiol 1993; 9:504.
  18. Whitehouse JD, Friedman ND, Kirkland KB, et al. The impact of surgical-site infections following orthopedic surgery at a community hospital and a university hospital: adverse quality of life, excess length of stay, and extra cost. Infect Control Hosp Epidemiol 2002; 23:183.
  19. Perencevich EN, Sands KE, Cosgrove SE, et al. Health and economic impact of surgical site infections diagnosed after hospital discharge. Emerg Infect Dis 2003; 9:196.
  20. Anderson DJ, Kaye KS, Chen LF, et al. Clinical and financial outcomes due to methicillin resistant Staphylococcus aureus surgical site infection: a multi-center matched outcomes study. PLoS One 2009; 4:e8305.
  21. Owens PL, Barrett ML, Raetzman S, et al. Surgical site infections following ambulatory surgery procedures. JAMA 2014; 311:709.
  22. Hughes JM, Culver DH, White JW, et al. Nosocomial infection surveillance, 1980-1982. MMWR CDC Surveill Summ 1983; 32:1SS.
  23. Delgado-Rodríguez M, Gómez-Ortega A, Sillero-Arenas M, Llorca J. Epidemiology of surgical-site infections diagnosed after hospital discharge: a prospective cohort study. Infect Control Hosp Epidemiol 2001; 22:24.
  24. CDC NNIS System. National Nosocomial Infections Surveillance (NNIS) report, data summary from October 1986- April 1998, Issued June 1998.
  25. Bratzler DW, Dellinger EP, Olsen KM, et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Surg Infect (Larchmt) 2013; 14:73.
  26. Anderson DJ, Podgorny K, Berríos-Torres SI, et al. Strategies to prevent surgical site infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol 2014; 35:605.
  27. https://www.cdc.gov/nhsn/pdfs/pscmanual/9pscssicurrent.pdf (Accessed on June 16, 2017).
  28. https://www.cdc.gov/nhsn/pdfs/pscmanual/9pscssicurrent.pdf (Accessed on April 06, 2017).
  29. Haley RW, Culver DH, Morgan WM, et al. Identifying patients at high risk of surgical wound infection. A simple multivariate index of patient susceptibility and wound contamination. Am J Epidemiol 1985; 121:206.
  30. Culver DH, Horan TC, Gaynes RP, et al. Surgical wound infection rates by wound class, operative procedure, and patient risk index. National Nosocomial Infections Surveillance System. Am J Med 1991; 91:152S.
  31. Mu Y, Edwards JR, Horan TC, et al. Improving risk-adjusted measures of surgical site infection for the national healthcare safety network. Infect Control Hosp Epidemiol 2011; 32:970.
  32. Henderson WG, Daley J. Design and statistical methodology of the National Surgical Quality Improvement Program: why is it what it is? Am J Surg 2009; 198:S19.
  33. Shahian DM, O'Brien SM, Filardo G, et al. The Society of Thoracic Surgeons 2008 cardiac surgery risk models: part 1--coronary artery bypass grafting surgery. Ann Thorac Surg 2009; 88:S2.
  34. Turan A, Mascha EJ, Roberman D, et al. Smoking and perioperative outcomes. Anesthesiology 2011; 114:837.
  35. Sørensen LT. Wound healing and infection in surgery: the pathophysiological impact of smoking, smoking cessation, and nicotine replacement therapy: a systematic review. Ann Surg 2012; 255:1069.
  36. Harris JE. Smoke yields of tobacco-specific nitrosamines in relation to FTC tar level and cigarette manufacturer: analysis of the Massachusetts Benchmark Study. Public Health Rep 2001; 116:336.
  37. Bodnar JA, Morgan WT, Murphy PA, Ogden MW. Mainstream smoke chemistry analysis of samples from the 2009 US cigarette market. Regul Toxicol Pharmacol 2012; 64:35.
  38. Sørensen LT. Wound healing and infection in surgery. The clinical impact of smoking and smoking cessation: a systematic review and meta-analysis. Arch Surg 2012; 147:373.
  39. Wukich DK, McMillen RL, Lowery NJ, Frykberg RG. Surgical site infections after foot and ankle surgery: a comparison of patients with and without diabetes. Diabetes Care 2011; 34:2211.
  40. Monfrecola G, Riccio G, Savarese C, et al. The acute effect of smoking on cutaneous microcirculation blood flow in habitual smokers and nonsmokers. Dermatology 1998; 197:115.
  41. Sørensen LT, Jørgensen S, Petersen LJ, et al. Acute effects of nicotine and smoking on blood flow, tissue oxygen, and aerobe metabolism of the skin and subcutis. J Surg Res 2009; 152:224.
  42. Black CE, Huang N, Neligan PC, et al. Effect of nicotine on vasoconstrictor and vasodilator responses in human skin vasculature. Am J Physiol Regul Integr Comp Physiol 2001; 281:R1097.
  43. Jensen JA, Goodson WH, Hopf HW, Hunt TK. Cigarette smoking decreases tissue oxygen. Arch Surg 1991; 126:1131.
  44. Møller AM, Villebro N, Pedersen T, Tønnesen H. Effect of preoperative smoking intervention on postoperative complications: a randomised clinical trial. Lancet 2002; 359:114.
  45. Sorensen LT, Karlsmark T, Gottrup F. Abstinence from smoking reduces incisional wound infection: a randomized controlled trial. Ann Surg 2003; 238:1.
  46. Møller AM, Kjellberg J, Pedersen T. [Health economic analysis of smoking cessation prior to surgery--based on a randomised trial]. Ugeskr Laeger 2006; 168:1026.
  47. Sørensen LT, Jørgensen T. Short-term pre-operative smoking cessation intervention does not affect postoperative complications in colorectal surgery: a randomized clinical trial. Colorectal Dis 2003; 5:347.
  48. Sørensen LT, Zillmer R, Agren M, et al. Effect of smoking, abstention, and nicotine patch on epidermal healing and collagenase in skin transudate. Wound Repair Regen 2009; 17:347.
  49. Sørensen LT, Toft B, Rygaard J, et al. Smoking attenuates wound inflammation and proliferation while smoking cessation restores inflammation but not proliferation. Wound Repair Regen 2010; 18:186.
  50. Sørensen LT, Toft BG, Rygaard J, et al. Effect of smoking, smoking cessation, and nicotine patch on wound dimension, vitamin C, and systemic markers of collagen metabolism. Surgery 2010; 148:982.
  51. Sørensen LT, Jorgensen LN, Zillmer R, et al. Transdermal nicotine patch enhances type I collagen synthesis in abstinent smokers. Wound Repair Regen 2006; 14:247.
  52. Reddy M. Skin and wound care: important considerations in the older adult. Adv Skin Wound Care 2008; 21:424.
  53. Fore J. A review of skin and the effects of aging on skin structure and function. Ostomy Wound Manage 2006; 52:24.
  54. Kluytmans J. Surgical infections including burns. In: Prevention and Control of Nosocomial Infections, Wenzel (Ed), Williams and Wilkins, Baltimore 1997. p.841.
  55. Kaye KS, Schmit K, Pieper C, et al. The effect of increasing age on the risk of surgical site infection. J Infect Dis 2005; 191:1056.
  56. Heinen MM, van Achterberg T, op Reimer WS, et al. Venous leg ulcer patients: a review of the literature on lifestyle and pain-related interventions. J Clin Nurs 2004; 13:355.
  57. Wilkinson EA. Oral zinc for arterial and venous leg ulcers. Cochrane Database Syst Rev 2012; :CD001273.
  58. Raffoul W, Far MS, Cayeux MC, Berger MM. Nutritional status and food intake in nine patients with chronic low-limb ulcers and pressure ulcers: importance of oral supplements. Nutrition 2006; 22:82.
  59. Arnold M, Barbul A. Nutrition and wound healing. Plast Reconstr Surg 2006; 117:42S.
  60. Abu-Rumman PL, Armstrong DG, Nixon BP. Use of clinical laboratory parameters to evaluate wound healing potential in diabetes mellitus. J Am Podiatr Med Assoc 2002; 92:38.
  61. Regan MA, Teasell RW, Wolfe DL, et al. A systematic review of therapeutic interventions for pressure ulcers after spinal cord injury. Arch Phys Med Rehabil 2009; 90:213.
  62. Wu SC, Crews RT, Armstrong DG. The pivotal role of offloading in the management of neuropathic foot ulceration. Curr Diab Rep 2005; 5:423.
  63. Haubner F, Ohmann E, Pohl F, et al. Wound healing after radiation therapy: review of the literature. Radiat Oncol 2012; 7:162.
  64. Payne WG, Naidu DK, Wheeler CK, et al. Wound healing in patients with cancer. Eplasty 2008; 8:e9.
  65. Cornell K, Waters DJ. Impaired wound healing in the cancer patient: effects of cytotoxic therapy and pharmacologic modulation by growth factors. Vet Clin North Am Small Anim Pract 1995; 25:111.
  66. Bootun R. Effects of immunosuppressive therapy on wound healing. Int Wound J 2013; 10:98.
  67. Wang AS, Armstrong EJ, Armstrong AW. Corticosteroids and wound healing: clinical considerations in the perioperative period. Am J Surg 2013; 206:410.
  68. Bosanquet DC, Rangaraj A, Richards AJ, et al. Topical steroids for chronic wounds displaying abnormal inflammation. Ann R Coll Surg Engl 2013; 95:291.
  69. Hofman D, Moore K, Cooper R, et al. Use of topical corticosteroids on chronic leg ulcers. J Wound Care 2007; 16:227.
  70. Erinjeri JP, Fong AJ, Kemeny NE, et al. Timing of administration of bevacizumab chemotherapy affects wound healing after chest wall port placement. Cancer 2011; 117:1296.
  71. Mendelsohn FA, Divino CM, Reis ED, Kerstein MD. Wound care after radiation therapy. Adv Skin Wound Care 2002; 15:216.
  72. Wang J, Boerma M, Fu Q, Hauer-Jensen M. Radiation responses in skin and connective tissues: effect on wound healing and surgical outcome. Hernia 2006; 10:502.
  73. Boffeli TJ, Thompson JC, Waverly BJ, et al. Incidence and Clinical Significance of Heterotopic Ossification After Partial Ray Resection. J Foot Ankle Surg 2016; 55:714.
  74. Brem H, Tomic-Canic M. Cellular and molecular basis of wound healing in diabetes. J Clin Invest 2007; 117:1219.
  75. Armstrong DG, Boulton AJM, Bus SA. Diabetic Foot Ulcers and Their Recurrence. N Engl J Med 2017; 376:2367.
  76. Santilli JD, Santilli SM. Chronic critical limb ischemia: diagnosis, treatment and prognosis. Am Fam Physician 1999; 59:1899.
  77. Singh N, Armstrong DG, Lipsky BA. Preventing foot ulcers in patients with diabetes. JAMA 2005; 293:217.
  78. Deatrick KB, Wakefield TW, Henke PK. Chronic venous insufficiency: current management of varicose vein disease. Am Surg 2010; 76:125.
  79. Kurd SK, Hoffstad OJ, Bilker WB, Margolis DJ. Evaluation of the use of prognostic information for the care of individuals with venous leg ulcers or diabetic neuropathic foot ulcers. Wound Repair Regen 2009; 17:318.
  80. Bowering CK. Diabetic foot ulcers. Pathophysiology, assessment, and therapy. Can Fam Physician 2001; 47:1007.
  81. Boulton AJ, Armstrong DG, Albert SF, et al. Comprehensive foot examination and risk assessment: a report of the task force of the foot care interest group of the American Diabetes Association, with endorsement by the American Association of Clinical Endocrinologists. Diabetes Care 2008; 31:1679.
  82. Trent JT, Kirsner RS. Leg ulcers in sickle cell disease. Adv Skin Wound Care 2004; 17:410.