Friend or Foe?
The Role of Inflammation in Wound Healing
Wound healing can be defined as an orderly, yet complex, repair of cells and tissue after injury. Wounding is a planned or unplanned event. Pressure or venous stasis ulcers are unplanned, where as elective surgery leaves an expected wound. Both go through the same complex, but orderly, series of events that culminate in a healed, scarred area. The first, and possibly most important, stage of wound healing is the inflammatory phase.
The inflammatory response begins immediately after tissue injury in most cases. Serving as a natural mechanism to alert the body that the wounded area needs to be treated differently, pain heralds the onset of the inflammatory response. The overall goal is to limit tissue injury. In the wound healing process, successful completion of this important first phase, normally lasting four to six days, is paramount to achieve eventual wound closure. This process can be viewed in a variety of ways - as a series of planned, orderly events coupled with cellular interactions; and clinically, in a bedside assessment.
- Events and Cellular Interactions - Platelets flood the injured area to achieve hemostasis and subsequently degranulate. Dumping growth factors into the area, with platelet derived growth factor (PDGF) being the most dominant, the inflammatory process begins. These growth factors are chemotatic - signaling cells to come to the area. Neutrophils, the first white blood cell type to arrive, release enzymes called proteases into the wound bed . Proteases function to rid the wound of cellular and tissue debris. Phagocytosis of bacteria is an ongoing process, first accomplished by neutrophils but then handed over to the next white blood cell to arrive - the monocyte. Once bacteria have been digested by the monocyte, it is then named a macrophage. The macrophage will release additional growth factors into the wound, serving to allow a normal transition to the second phase of wound healing, known as the proliferative stage. Additonal inflammatory cytokines, namely, TNF-α and IL-1β, are secreted. Besides activating fibroblasts needed for proliferation, they also continue to secrete proteases to keep the wound free of cellular and tissue debris. As the inflammatory process resolves, enzyme inhibitors enter the wound to “shut off” enzyme activity and transition the wound to the proliferative phase.
- Clinical Bedside Exam - As important as it is to understand the physiology of the inflammatory phase, it is also important to recognize its normalcy during routine assessment. Platelets plugs, seen as clots, may be visible. One- half to one centimeter of diffuse light pink erythema around the wound which is mildly indurated, or hard, to touch might be present during the initial post-operative days. When palpated, this area feels similar to the tip of one’s nose. Additionally, mild warmth will be felt. This should resolve within approximately 6-10 days after wounding. In surgical wounds, the inflammatory process presents in a similar manner.
If inflammation is good, how can it be bad? As in dosing medication, too little or too much inflammation is detrimental. Deficient and, on the contrary, excess inflammation can be viewed using the same framework - events and cellular interactions, as well as the clinical bedside exam.
- Events and Cellular Interactions - If no inflammatory response is triggered, or is severely blunted, the wounded area receives no or minimal signals to recruit white blood cells to the area. Reduced numbers of neutrophils and monocytes allow bacteria to proliferate. Cellular and tissue debris build up in the wound. When excessive inflammation is present, proteases are no longer selective against debris. They degrade growth factors, receptor sites on cells and prevent fibroblasts and other wound healing cells from functioning normally. The wound is unable to enter the proliferative phase of wound healing. A state of elevated and persistent inflammation develops. Inhibitory chemicals normally available to “turn off” the cytokines responsible for the inflammation do not get activated, creating a vicious cycle.
- Bedside Clinical Exam - In the presence of decreased or absent inflammation, little to no erythema is visible around the wound. The wound will not be clean and healthy looking. It is often pale with shreds of fibrin - a yellowish white sticky adherent coating- on the wound. Necrotic tissue and pus may also be seen. Excessive inflammation can happen in all stages of wound healing so identifying the wound with these traits is a bit trickier. In this scenario, too much inflammation is categorized as chronically inflamed or acutely inflamed. The excessive but acutely inflamed wound appears with classic signs of infection - hard, warm, red, and painful tissue in and around the wound. The chronically inflamed wound has more subtle signs. Look at the following: wound measurements, drainage and the tissue characteristics. Specifically, a wound whose measurements have not decreased in the previous two weeks, has excessive drainage with or without odor, and a wound bed that displays a healthy red tissue that is often smooth and clean with friability (i.e. bleeds easily). To test for friability, use a cotton swab to touch the wound bed. If it bleeds easily or there is blood on the swab, the friability test is positive. Any time that wound measurements increase this usually signifies that the wound is shifting from the chronically inflamed to an acutely inflamed wound. Lastly, granulation, usually seen as small mounds of puffy red tissue, is absent.
What kind of influence does the bedside clinician have in controlling the inflammatory response? Several nursing interventions facilitate a normal inflammatory response. First, it is important to identify patient risk factors placing a wound at risk for abnormal inflammation. While this list is not all inclusive, it represents the most common reasons for inflammatory impairment.
- Immunosupressive medications. Patients receiving oral steroids, chemotherapeutic agents, anti-rejection agents, and NSAIDs place the wound at risk for blunted or absent inflammation. To evaluate if a patient can mount a normal inflammatory response, the clinician can calculate the Total Lymphocyte Count (TLC). To do this, a complete blood count (CBC) with differential is necessary. Apply the following formula:
White Blood Cell count (WBC) X 10 X % of Lymphocytes in differential
A TLC over 2000 is normal. One would expect a normal inflammatory response. Mild (a TLC between 1200 and 2000) and moderate (TLC = 800-1200) reductions correlate with delayed wound healing. A TLC of 800 or less correlates with poor or absent wound healing.
- Uncontrolled Diabetes. Excessive glucose levels render white bloods cells inefficient in their function. In addition to slowing their mobility through tissue, high blood glucose levels impair the white blood cell’s ability to phagocytotize bacteria and produce chemical signals that continue the wound healing process.
- Excessive bacteria. Open wounds become contaminated shortly after the injury. Likewise, open wounds will become colonized within 3 days. What’s the difference? In a contaminated wound, the bacteria are not attached to the wound bed. Colonized wounds have bacteria attach themselves to the wound bed and is a natural phenomena. This becomes detrimental to wound healing when bacteria replicate. Research has shown that bacterial levels of 102 have shown to enhance the normal inflammatory process. Levels greater than 105 or the presence of Beta Hemolytic Streptococcus promote excessive, persistent inflammation. Excessive bacteria increase the production of proteases.
A number of interventions are available for bedside clinicians that promote a normal inflammatory response. Employing these can help achieve wound closure.
- Wound Irrigation. Wound irrigation should occur at every wound dressing change in the case of an open wound or one healing by secondary intention.. Using a non-cytotoxic solution, such as normal saline, in the specified pressure range of 4-15 pounds per square inch (psi) clears the wound of the byproducts of cellular and tissue debris. Although many commercial products are available that apply the correct psi, a 60 cc piston syringe usually will suffice. Be generous in irrigation, using at least 50 cc per square centimeter of wound surface.
- Controlling blood glucose levels. Aggressive management, through patient education and medications, is key to normalizing this important factor.
- Adjust or eliminate medications that inhibit inflammation. This is the toughest task, as many patients require these to maintain current function and health. Discussion with the patient’s physician is imperative. If no adjustments can be safely made, consider changing the goal from wound healing, to that of preventing acute infection and maintaining the wound in its present state.
- Eliminate factors that increase protease production. In addition to bacterial control though irrigation, the application of topical antimicrobial agents, improving perfusion, reducing mechanical forces such as shear and pressure, controlling wound exudate, and managing edema are helpful. The use of topical agents, such as ORC/Collagen, that actively remove proteases has been shown to improve the local wound environment and promote healing.
- Debridement. While debridement has been well recognized as helpful in removing necrotic tissue, the use of bedside conservative sharp debridement in a clean wound with a curette or scalpel is another method that correlates with reducing excessive, persistent inflammation. Individual licensing requirements vary between states, but it is generally accepted that advanced practice nurses and physical therapists can provide these services in addition to physicians. Collaborate with these clinicians to provide these services.
To summarize, the right balance of inflammation is necessary to promote wound healing. A number of nursing interventions, easily implemented in the home health setting, can harness inflammation - transforming foe into friend.
This article was written by Catherine T. Milne APRN, MSN, BC, CWOCN