Journal of Gerontological Nursing

CLINICAL OUTLOOK 

Nursing Experience Using Growth Factors In Nonhealing Wound Repair

Margaret A McMahon, MS, RNC

Abstract

Chronic, nonhealing skin ulcers are a significant health care problem. As both the number oí elderly people and the incidence of such diseases as diabetes mellitus, venous insufficiency, and the loss of mobility due to aging or neurologic deterioration increase, the number of chronic nonhealing wounds also increases. Advances in the understanding of bioregulation of normal wound repair, however, are providing new treatment modalities to stimulate or accelerate the repair of chronic nonhealing wounds. One treatment modality is the use of growth factors derived from platelets.

REVIEW OF THE UTERATURE

Studies have demonstrated that macrophages and platelets are the predominant cells in the repair process. Platelets are known to contain at least five growth factors that result in granulation tissue formation and epithelialization: platelet-derived angiogenesis factor, which causes new capillary formation from existing microvasculature; platelet-derived growth factor, a fibroblast mitogen and chemoattractant; platelet-derived epidermal growth factor, which causes migration and mitosis of epidermal cells; transfonning growth factor-ß, a chemoattractant for monocytes that inhibits endothelial cell mitosis, inhibits fibroblast mitosis at certain concentrations, and stimulates collagen and giycosaminoglycan synthesis; and platelet factor 4, a chemoattractant for neutrophils (Antoniades, 1979; Deuel, 1981; Grotendorst, 1985; Knighton, 1982; Oka, 1983; Ross, 1974, 1987; Sporn, 1987; Wahl, 1987) (Table 1).

CUNICAL PROTOCOL

Although patients with chronic wounds have different underlying health problems, such as venous insufficiency or diabetes mellitus, the clinical protocol for treating their wounds is similar. First, a complete history and physical examination by the attending physician is done. Oral antibiotic therapy usually is prescribed for 10 days before the inauguration of growth-factor therapy, because superficial infections may be present without significant invasion. Another prescription may be Trental (pentoxifylline) 400 mg three times a day with meals to enhance blood flow and subsequently wound healing.

Because wounds at the foot/lower leg are common, arrangements for modifications in lifestyle for some patients may be initiated. Nonweight-bearing ambulation has been found to be a critically important element for woundhealing success - especially in the early weeks of treatment (Steed, 1991). Further, patients should be advised to elevate the affected limb on a pillow when sitting or lying in bed to enhance circulation. The body temperature must be checked daily as a monitor for infection.

Nutritional Needs

Before initiation of platelet-derived wound healing formula (PDWHF) therapy, a 3-day dietary history is obtained and reviewed to identify the existence of deficiencies and ultimately to implement a plan of correction as indicated. Specifically, the nutritional needs necessary to facilitate wound healing are found in a diet that includes vitamins A, B complex, and C; is high in protein and carbohydrates; and maintains a moderate fat intake (Table 2).

Protein is needed to correct the negative nitrogen balance resulting from the increased metabolic rate and synthesis of immune factors, leukocytes, fibroblasts, and collagen. Carbohydrates are needed for increased metabolic energy required in healing. Fats help in the synthesis of fatty acids and triglycerides that are a part of the cellular membrane. Vitamin A aids in the process of epithelialization by increasing collagen synthesis and tensile strength of the healing wound. The B complex vitamins are necessary as enzymes for many metabolic reactions. Vitamin C is necessary for capillary synthesis, capillary formation, and resistance to infection (Lewis, 1992).

Suggestions should be made both to patients and their families about the importance of eating a proper variety of foods every day. A part of the nursing care plan is to monitor daily food intake, which includes encouraging patients to consume supplemental nutrition (snacks), such as fruit, fruit juices, and dairy products between meals and at bedtime as a support for attaining…

Chronic, nonhealing skin ulcers are a significant health care problem. As both the number oí elderly people and the incidence of such diseases as diabetes mellitus, venous insufficiency, and the loss of mobility due to aging or neurologic deterioration increase, the number of chronic nonhealing wounds also increases. Advances in the understanding of bioregulation of normal wound repair, however, are providing new treatment modalities to stimulate or accelerate the repair of chronic nonhealing wounds. One treatment modality is the use of growth factors derived from platelets.

REVIEW OF THE UTERATURE

Studies have demonstrated that macrophages and platelets are the predominant cells in the repair process. Platelets are known to contain at least five growth factors that result in granulation tissue formation and epithelialization: platelet-derived angiogenesis factor, which causes new capillary formation from existing microvasculature; platelet-derived growth factor, a fibroblast mitogen and chemoattractant; platelet-derived epidermal growth factor, which causes migration and mitosis of epidermal cells; transfonning growth factor-ß, a chemoattractant for monocytes that inhibits endothelial cell mitosis, inhibits fibroblast mitosis at certain concentrations, and stimulates collagen and giycosaminoglycan synthesis; and platelet factor 4, a chemoattractant for neutrophils (Antoniades, 1979; Deuel, 1981; Grotendorst, 1985; Knighton, 1982; Oka, 1983; Ross, 1974, 1987; Sporn, 1987; Wahl, 1987) (Table 1).

CUNICAL PROTOCOL

Although patients with chronic wounds have different underlying health problems, such as venous insufficiency or diabetes mellitus, the clinical protocol for treating their wounds is similar. First, a complete history and physical examination by the attending physician is done. Oral antibiotic therapy usually is prescribed for 10 days before the inauguration of growth-factor therapy, because superficial infections may be present without significant invasion. Another prescription may be Trental (pentoxifylline) 400 mg three times a day with meals to enhance blood flow and subsequently wound healing.

Because wounds at the foot/lower leg are common, arrangements for modifications in lifestyle for some patients may be initiated. Nonweight-bearing ambulation has been found to be a critically important element for woundhealing success - especially in the early weeks of treatment (Steed, 1991). Further, patients should be advised to elevate the affected limb on a pillow when sitting or lying in bed to enhance circulation. The body temperature must be checked daily as a monitor for infection.

Nutritional Needs

Before initiation of platelet-derived wound healing formula (PDWHF) therapy, a 3-day dietary history is obtained and reviewed to identify the existence of deficiencies and ultimately to implement a plan of correction as indicated. Specifically, the nutritional needs necessary to facilitate wound healing are found in a diet that includes vitamins A, B complex, and C; is high in protein and carbohydrates; and maintains a moderate fat intake (Table 2).

Protein is needed to correct the negative nitrogen balance resulting from the increased metabolic rate and synthesis of immune factors, leukocytes, fibroblasts, and collagen. Carbohydrates are needed for increased metabolic energy required in healing. Fats help in the synthesis of fatty acids and triglycerides that are a part of the cellular membrane. Vitamin A aids in the process of epithelialization by increasing collagen synthesis and tensile strength of the healing wound. The B complex vitamins are necessary as enzymes for many metabolic reactions. Vitamin C is necessary for capillary synthesis, capillary formation, and resistance to infection (Lewis, 1992).

Suggestions should be made both to patients and their families about the importance of eating a proper variety of foods every day. A part of the nursing care plan is to monitor daily food intake, which includes encouraging patients to consume supplemental nutrition (snacks), such as fruit, fruit juices, and dairy products between meals and at bedtime as a support for attaining optimal nutrition for wound healing.

Table

TABLE 1Growth Factors that Cause Granulation Tissue Formation

TABLE 1

Growth Factors that Cause Granulation Tissue Formation

Table

TABLE 2Nutritional Measures to Facilitate Wound Healing

TABLE 2

Nutritional Measures to Facilitate Wound Healing

Alternating Applications (PDWHF-AnKbioric Solution)

Wounds usually are débrided in ambulatory surgery to remove all nonviable soft and hard tissue from the ulcer before initiation of PDWHF treatments. Procuren solution, a PDWHF, is used as a wet-to-dry dressing applied once a day and left on the wound for 12 hours.

Careful handwashing, donning treatment gloves, and establishing and maintaining a clean environment are important steps before cleaning the wound gently with warm tap water and patting it dry with a clean gauze pad. A gauze pad that will cover the entire wound base is saturated with Procuren and placed evenly into or over the wound (but not overlapping its edges).

A petrolatum-impregnated gauze dressing larger than the wound is placed as a cover over the gauze on the wound. The edges of the petrolatum gauze should be pressed gently onto the skin to create a seal. This decreases evaporation of Procuren and helps keep the wound moist. Dry gauze sponges are placed over the petrolatum gauze, and the limb is wrapped with a bulky stretch bandage (eg, Kerlex) to keep the sponges in place. Paper tape is used on the bandage only to secure it in place. A stretch wrap, such as an Ace wrap, is applied to the foot or lower leg to enhance circulation.

To keep the wound moist and reduce infections, an alternate dressing/ medicine is used for the remaining 12 hours of each day. The Procuren dressing should be carefully removed, and the wound irrigated with warm tap water and dried. An effective alternate dressing is a gauze pad moistened with Triple Antibiotic Solution (clindamycin, gentamicin, polymyxin), Silvadene (silver sulfadiazine), or normal saline (Atri, 1990; Knighton, 1986). The pad is applied to the wound and the wound is covered and wrapped for the next 12 hours.

These alternating treatment applications continue every 12 hours. Wound parameters and the extent of epithelialization are checked and recorded every day by the nurse and once a week by the physician. Some indicators of healing are red tissue in the base of the wound that bleeds easily as new vessels are forming, and a 1/4 inch reddened area around the perimeter of the wound that is due to increased blood vessels and blood flow as one of the growth factors stimulates angiogenesis (Figure). This reddened area could be mistaken for erythema, so it is important to assess for other signs of infection. An extension of the reddened area beyond 1 /4 inch should not occur.

DISCUSSION

The changes in wound dimensions after initiation of the PDWHF therapy are slow for the first weeks. A sharp decrease in wound dimensions does not come until toward the end of the treatment, when the wound is almost healed (Knighton, 1989).

Concerns that the treatment is failing may prompt patients to request more frequent applications of PDWHF to "speed things up." A reminder must be given to patients that the growth factors give the cells the message to move into place and reproduce, thereby filling the wound with capillaries and new tissue. Once a cell receives a message, it is too busy acting on that message to be able to accept additional instructions for about 24 hours. Thus, PDWHF applications that are more frequent than once-a-day would be of no benefit. It is an important time, however, for nurses to listen carefully to patients'/families' concerns and be a source of stable, knowing support.

The rate of healing varies with the disease underlying the ulceration. It has been found that wounds due to venous stasis need a longer time to heal (21 weeks) than those associated with diabetes (10 weeks) (Atri, 1990).

Figure. Early stages of healing wound on toe that healed in 14 weeks. (Photo courtesy of Curative Technologies, Inc.)

Figure. Early stages of healing wound on toe that healed in 14 weeks. (Photo courtesy of Curative Technologies, Inc.)

Discharge Planning

Instructions must be given to patients and their families regarding proper handwashing techniques, establishing and maintaining a clean environment, meticulous wound care, nutrition, blood sugar control (for diabetics), exercise, foot care guidelines, and prevention of injury to extremities by wearing appropriate foot gear. The long-range goal is to prevent recurrence of the ulcers after the healing process.

Some older patients may be mtimidated by the prospect of self-care/treatment. Therefore, arrangements should be made before their discharge to have home health care nurses continue the treatment regimen. Clinic evaluations are scheduled for every week and eventually every 2 weeks if progress is satisfactory. Patients and families are cautioned to call the home health nurse or physician immediately if there are any changes in the appearance of the wound, such as redness, warmth, pain, swelling, foul smelling, creamy discharge, or other indications of infection.

SUMMARY

The use of growth factor derived platelets represents an intensive effort to repair difficult, nonhealing cutaneous ulcers in a safe manner, improvements have been seen in patients treated with growth factors. The nurse's role as a knowledgeable and contributing member of the treatment team is imperative to the success of the prescribed regimen.

REFERENCES

  • Antoniades, H.N., Scher, CD., Stiles, CD. Purifications of human platelet derived growth factor. Proc Natl Acad Sci USA 1979; 76(4): 18091813.
  • Atri, SC, Misra, J., Bisht, D., Misra, K. Use of homologous platelet factors in achieving total healing of recalcitrant skin ulcers. Surgery 1990; 108(3):508-512.
  • Deuel, T.F., Senior, R.M., Chang, D., Griffin, G.L., Heinrikson, R.L., Kaiser, ET. Platelet factor 4 is chemotactic for neutrophils and monocytes. Proc Natl Acad Sci USA 1981; 78(7):45844587.
  • Grotendorst, CR., Martin, CR., Pencev, D., Sodek, J., Harvey, A.K. Stimulation of granulation tissue formation by platelet-derived growth factor in normal and diabetic rats. / Clin Invest 1985; 76:2323-2329.
  • Knighton, D.R., Ciresi, K.F., Fiegel, V.D., Austin, L.L., Butler, E.L. Classification treatment of chronic nonhealing wounds: Successful treatment with autologous platelet-derived wound healing factors (PDWHF). Ann Surg 1986; 204:322-330.
  • Knighton, D.R., Fylling, CP., Doucette, M.M. Wound healing and amputation in a high risk diabetic population. Wounds: A Compendium at Clinical Research and Practice 1989; 1(2):108-114.
  • Knighton, D.R., Hunt, T.K., Thakral, K.K., Goodson, W.H. Role of platelets and fibrin in the healing sequence: An in vivo study of angiogenesis and collagen synthesis. Ann Surg 1982; 196:379-388.
  • Lewis, S.M., Collier, I.C Medicalsurgical nursing, 3rd ed. St. Louis: Mosby-Year Book, 1992.
  • Oka, Y., Orth, D.N. Human plasma epidermal growth factor/Burogastrone is associated with blood platelets. / Clin Invest 1983; 72:249-259.
  • Ross, R. Platelet-derived growth factor. Annals and Reviews of Medicine 1987; 38:71-79.
  • Ross, R., Glomest, J., Kariya, B., Harker, L. A platelet dependent serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro. Proc Natl Acad Sci USA 1974; 71(4):1207-1210.
  • Sporn, M.B., Roberts, A.B., Wakefield, L.M., deCrombrugghe, B. Some recent advances in the chemistry and biology at transforming growth factor-beta. / Cell Biol 1987; 105:1039-1045.
  • Steed, D., Goslen, B., Hambley, R., Abell, E., Hebda, R, Webster, M. Clinical trials with purified platelet releasate. Prog Clin Biol Res 1991; 365:103-113.
  • Wahl, S.M., Hunt, D.A., Wakefield, L.M., McCartney-Francis, N., Wahl, L.M., Roberts, A.B., Sporn, M-B. Transforming growth factor type beta induces monocyte Chemotaxis and growth-factor production. Proc Natl Acad Sci USA 1987; 84(16):5788-5792.

TABLE 1

Growth Factors that Cause Granulation Tissue Formation

TABLE 2

Nutritional Measures to Facilitate Wound Healing

10.3928/0098-9134-19940901-11

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