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Wound Healing

Carl Gorman BVSc MRCVS

 

Cutaneous wounds

Skin wounds of many types are a common presentation in veterinary practice.  They will normally result from trauma which may be from bites, accidents, abrasions, burns, ulcers or self trauma.  Less commonly wounds may result from a disease process (e.g. vasculitis, auto-immune disease, loss of skin elasticity and strength in endocrine disease).  Wounds which are closed surgically leaving no areas without skin cover can be considered as surgical wounds, which heal by primary intention.  Surgical wounds will still pass though the same stages of wound healing, but these will be much less obvious as primary intention healing means that the wounds stay closed.  The focus of this article is open wounds, which will heal by secondary intention, either to resolution or until they are suitable for conversion to a surgical wound.

When managing skin wounds it is important to understand the processes involved in healing, and the potential timescales involved.

Normal wound healing

There are three phases of normal healing.

                Inflammatory phase

                This lasts for 24 - 48 hours.

                The phase begins with haemostasis.  Platelets form a thrombus.  They release growth factors which induce chemotaxis of neutrophils and macrophages and stimulate their proliferation.  These cells cooperate to remove bacteria, debris and necrotic tissue from the wound.  Macrophages become the most numerous cell in this phase, and they release growth factors and cytokines which encourage cell formation in the wound.  (Fig 1)

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Fig 1 Healing after vertical canal ablation surgery.  At 2- 3 days post trauma, whether surgical or accidental, wounds are in the inflammatory phase and can look at their worst.

                 Proliferative phase

                This phase lasts for 2 to 3 weeks.

                In this phase fibroblasts are the dominant cell.  They produce collagen which gives structure and strength to the wound, and replaces the fibrin which has sealed the wound up until now.  Angiogenesis creates capillaries which sustain the fibroblast proliferation.  A healthy granulation bed forms - this has a granular texture and is red or pink in colour.  Healthy granulation tissue is very resistant to infection.  Keratinocytes reepithelialise the wound. (Fig 2, Fig 3, Fig 4)

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Fig 2 A wound which wasn't healing after a cat bite.  Infection and self-trauma are two factors leading to delayed healing.

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Fig 3 The wound was treated with laser therapy, antibiotics and a hydrogel dressing.  An Elizabethan collar prevented self-trauma.  At Day 5, the proliferative phase of healing is well under way, with healthy granulation tissue.  There is already epithelialisation.

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Fig 4  At Day 10 epithelialisation is complete and the wound enters the maturation phase.  The scar will remodel and contract over time.

 

                 Remodelling or maturation phase

                This phase can last up to two years.

                Once epithelialisation has occurred, fibroblasts organise and cross link the collagen, increasing wound strength.  Wound contraction occurs.  The wound loses its pink or purple colour as capillary and fibroblast numbers increase.

Any of these phases can be prolonged by a number of factors.  The commonest are infection, poor nutrition, external abrasion and factors such as endocrine disease which affect the normal pattern of the healing phases.  Clients and veterinarians are often impatient for wounds to heal - in human medicine the definition of a chronic wound is one that has not healed after 3 months.

We may intervene at various stages of the process.  For example once a wound has contracted and granulated it may be converted to a surgical wound and closed, or a skin graft may be used.

Management

The aim of management of wounds is to remove debris and necrotic material, avoid infection and provide the optimum environment for the healing phases to proceed.  Analgesia should not be neglected as many open wounds are a source of considerable discomfort.

                Cleaning and debriding

After initial assessment of the patient for other more significant trauma, and of the wound to determine its nature, cleaning of the wound should be carried out.  The wound should be protected with a water soluble gel (e.g. KY Gel) and the surrounding area clipped.  This reduces further contamination and allows further assessment of the area of damage.  (Fig 5)

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Fig 5  A fresh wound.  This will need to be managed by clipping the surrounding fur and lavage before attempting repair.

                 Cleaning is achieved by flushing.  Hartmann's solution or lactated Ringer's is the most suitable as it has no cytotoxic effect.  Although normal saline does have a degree of cytotoxity due to its acidity, it is better to flush with saline or even tap water than to do nothing.  Opinion is divided over the use of antiseptic solutions such as chlorhexidine.   Some experts feel that the cytotoxic effects of chlorhexidine outweigh the possible benefits of its antibacterial effect, and that it has no residual effect in contaminated wounds.  Others still advocate the use of mild solutions (less than 0.05%) for wound flushing.  25mls of 2% chlorhexidine in a litre bag of fluid gives a concentration just under 0.05%.  One study showed no difference in bacterial levels in contaminated wound flushed with 0.05% chlorhexidine or with saline.

                Cleaning is best achieved by copious flushing.  A pressure of 8 psi (pounds per square inch) is ideal.  This is enough pressure to achieve cleaning and dislodgement of contaminated material.  Higher pressures will cause tissue damage and may drive contaminants further into a wound.  Tissue damage must be avoided because it will delay healing, and also reduce the wound's ability to defend itself against infection.  A flush pressure of 8 psi can be achieved by using a 30 ml syringe and an 18G needle.  This can be attached to a litre bag of Hartmann's with a giving set and a three way tap.  Canned flush solution which sprays fluid at the correct pressure can also be bought.

                Necrotic material should be removed by surgical debridement and then by the use of suitable dressings.  Dry-to-dry and wet-to-dry dressings are both suitable, though the latter are more often used.  For wet-to-dry dressings gauze swabs are soaked in saline or Hartmann's and excess moisture is squeezed out.  The swab is applied to the wound and covered with an absorbent dressing, then an outer layer to keep it in place.  Proteinaceous exudate soaks into the swab.  Once dry, the dressing is removed taking non-vital necrotic material with it.  These dressings should be changed once or twice daily.  They can be uncomfortable to remove, so sedation or even general anaesthesia may be required.  These are not used in human medicine now because of the discomfort involved in changing the dressings, and should be used sparingly if at all in veterinary medicine.

                Gentler debridement can be achieved by using hydrogels over the wound with a non-adherent dressing.  These encourage debridement by autolysis.  They can be left in place for 48 hours.  A variety of covering dressings are available and the choice of which to use will depend on the degree of exudate from the wounds, and the stage of healing.

                Medical grade honey can also be used over open wounds.  Honey has antibacterial and anti-inflammatory properties which can be helpful.  It is important to use medical grade honey, which has been irradiated to sterilise it.  Regular food grade honey can contain bacterial spores (e.g. Clostridia species) which can contaminate a wound.  One way in which honey works is by releasing low levels of hydrogen peroxide, sufficient to have an antibacterial effect, but not to damage fibroblasts and epidermal cells.  Manuka honey contains additional chemicals which are also affective at disinfecting wounds.  Dressings impregnated with honey are available. 

                Wound contraction and epithelialisation

                Debridement should be carried out until all non-vital tissue is removed and a healthy bed of granulation tissue has developed.  This is a uniform red tissue which bleeds readily.  A fully granulated wound is resistant to infection.  At this stage the wound can be converted to a surgical wound and closed, a graft can be placed or the wound can be left heal by secondary intention.

                If the wound is to be allowed to heal by secondary intention, it should be covered with non-adherent dressings to avoid removing new epithelial cells when the dressings are removed.  A moist environment is best to encourage new skin growth.  Hydrogels can be used to achieve this, but they can also be associated with excessive granulation tissue, so the wound needs careful monitoring.  The skin around the edge of the wound should be kept dry to avoid maceration.  Maceration is the softening or decomposition of tissue by contact with liquid, and will hinder the healing process or even weaken the wound area.  (Fig 6)

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Fig 6  After clipping and lavage the wound will be ready for further management.  This may involve primary closure or dressings to allow debridement and formation of a healthy granulation bed.

                 However wounds heal, whether by primary or secondary intention, there will be a scar at the site of healing, which becomes stronger with time.  Scar tissue will never reach the same level of strength as original skin tissue. It will probably attain 80% of the original strength, and this may take one to two years to be achieved.  (Fig 7) 

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Fig 7  Surgical wounds, such as this castration wound, will benefit from post op laser treatment.  This reduces pain and swelling, speeds healing and promotes a stronger scar.

Factors affecting wound healing

It can be seen from the timescales quote above that it can take several weeks for a wound to be covered by new skin, and once the initial epithelialisation has taken place it could be two years before the final remodelling of the wound has completed.  Patience is needed, particularly when dealing with open wounds, and it is important to understand what is normal and when a wound is not responding as expected.

Factors which may adversely affect wound healing include: 

  • Location of the wound
    • E.g. if the wound is located in area of excess movement, such as an elbow.
  • Interference with the wound
    • Generally by the patient licking, chewing or interfering with dressings.
  • Poor blood supply (lack of oxygen and nutrients)
    • Damage to the vascular supply at the time of trauma.
    • Poor bandaging technique applying excess pressure.
    • Poor grafting technique leaving the graft with a compromised blood supply.
    • Circulatory disease, vasculitis, thrombosis.
    • Anaemia.
  • Infection
    • Failure to deal with initial contamination.
    • Infection during healing.
  • Metabolic disorders
    • Hyperadrenocorticism.
    • Hypothyroidism.
    • Diabetes mellitus.
    • Hypoalbuminaemia.
    • Malnutrition.
    • Renal disease (uraemia slows formation of granulation tissue and good quality collagen).
  • Necrotic material in the wound
    • Insufficient debridement.
    • Tissue necrosis through compromised blood supply, poor bandaging, insufficient bandage changes.
  •  Iatrogenic
    • Corticosteroids.
    • Toxic agents used for cleaning or dressing the wound.

Although there are many influences on wound healing, some basic rules will ensure that the vast majority of wounds heal successfully.

  • Proper initial assessment
  • Protection from unnecessary contamination
  • Thorough flushing to remove all debris and reduce contamination
  • Thorough debridement
  • Management of infection
    • Though remember that many wounds don't require antibiotics, and a granulated wound is very resistant to infection
  • Appropriate dressings and bandaging technique
  • Management of any secondary factors, such as concomitant disease, and appropriate nutrition
  • Patience

(Fig 8, Fig 9, Fig 10)

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Fig 8  Pressure from a dressing over a fractured radius and ulna caused this wound on a carpus.

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Fig 9  Day 4.  Removing the pressure and daily laser therapy encouraged healing and epithelialisation.

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Fig 10 Day 8     Epithelialisation is almost complete.

Effect of laser therapy on wound healing

Low level laser treatment (LLLT) is a relatively recent technique in veterinary medicine, but has been used in human medicine for management of wounds for over 20 years.

There are now numerous studies in humans and animals, in surgical and non-surgical wounds, demonstrating the benefits of LLLT in wound management.  The benefits include:

  • Speeding healing of traumatic injuries by 25-35%.
  • Stimulating the production of granulation tissue.
  • Stimulating the division of cells in the germinal layer of the epidermis, and so speeding up epithelialisation.
  • Reduction of inappropriate inflammatory responses which slow healing.
  • Reducing the time of suture removal (in a study on rabbits) to 6 days as opposed to at least 10 days in the control group.
  • Improving the appearance of scars after healing

There are also studies where no benefit has been shown compared to controls and this may be because there are many different wavelengths of laser which can be used, and by varying the time of application, the frequency of any pulsing, and the intensity used, there can be a huge variation in the energy delivered to a wound.  As experience grows and more studies are carried out, we will perfect the optimum treatment regimes.

All of the above benefits together with a reduction in pain and swelling can be achieved with post-operative laser treatment of surgical wounds.  Studies have shown improved quality of collagen in scars 14 days after surgery when laser was used.

Studies have shown reduced proliferation of bacteria (e.g. MRSA Staphylococcus aureus) in wounds treated with laser compared to controls.  Other studies have shown no difference between treated wounds and untreated wounds.  Again, this may reflect the different methods of laser delivery and is an area which needs further research.

It is important to follow the manufacturer's guidelines when using LLLT to treat wounds.  Settings for wounds will normally be noticeably shorter than those used for arthritis or for muscle disorders.  The aim is to achieve stimulation of the cells and tissues involved without using excess energy.

As a guide, when treating open wounds which will heal by secondary intention, use a wound setting and treat daily until there are signs that the inflammatory phase of healing has passed and proliferation is taking place.  Then reduce the frequency of treatments until epithelialisation has completed.   (Fig 11, Fig 12, Fig 13)

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Fig 11 This ulcer in the pad of a Leonburger had been treated for months with dressings and antibiotics.  There had been an initial traumatic wound which healed as far as this ulcer but then healing stopped.  Whenever the dog walked, the lesion would bleed, and it was uncomfortable.  Laser treatment using the MLS laser was started every other day.

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Fig 12 Day 4.  The ulcer was comfortable and bleeding had stopped.  The healing process had resumed.  Laser treatment was reduced to twice weekly.

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Fig 13  Day 27.  Healing had completed.