WOUND MANAGEMENT. HOW WOUNDS HEAL And Why Some Don t Heal Quality Pharmacy Training Chronic Wound Delayed Healing 4/20/2017

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1 WOUND MANAGEMENT Medicine, Nursing and Health Sciences HOW WOUNDS HEAL And Why Some Don t Heal Quality Pharmacy Training 2017 Associate Professor Geoff Sussman Clayton Campus PRIMUM NON NOCERE The first thing, do no harm! "The Provision of the Appropriate Environment for Healing by both Direct and Indirect Methods Together with the Prevention of Skin Breakdown Sussman Geoff Sussman Austin & Repatriation Medical Centre Phases of Healing Inflammatory phase shortest phase bleeding clotting for haemostasis surrounding erythema, heat, pain (may not be infection) exudate manifest Destructive actions Phagocytosis protease destruction of tissue growth factor release Proliferative phase angiogenesis collagen deposition fibroblast activity contraction, granulation, epithelisation Maturation tensile strength develops may take many months Normal Wound Healing Acute tissue Platelet degranulation Release of GF injury Inflammation with influx of neutrophils and macrophages Kill Bacteria Release of Proteases from Neutrophils Activation of macrophages with release of cytokines and growth factors Debridement TNF and IL-1 Growth Factors Influx of Fibroblasts and Endothelial Cells Collagen Synthesis Angiogenesis Scar formation, Epithelialization, Remodeling Mast BA & Schultz GS ( 1996 ) Repeated Trauma Local Tissue Ischemia Necrotic Tissue Heavy Bacterial Burden Tissue Breakdown Degrades ECM impaired cell migration impaired connective tissue deposition Degrades Growth Factors Chronic Wound Delayed Healing Prolonged Inflammation Stimulation of macrophage and neutrophils to wound bed Activation of macrophages with release of cytokines TNF and IL-1 WOUND MANAGEMENT TRADITIONAL THEORY 1. WOUNDS SHOULD BE KEPT CLEAN AND DRY SO THAT A SCAB FORMS OVER THE WOUND 2. WOUNDS SHOULD BE EXPOSED TO AIR AND SUNLIGHT AS MUCH AS POSSIBLE 3. WHERE TISSUE LOSS IS PRESENT THE WOUND SHOULD BE PACKED TO PREVENT SURFACE CLOSURE BEFORE THE CAVITY IS FILLED 4. WOUNDS SHOULD BE COVERED WITH A DRY DRESSING 3 Mast BA & Schultz GS (1996 ) Production MMPs and TIMPs 1

2 TRADITIONAL THEORY DISADVANTAGES MOIST WOUND MANAGEMENT GEORGE WINTER Nature 20/1/62 1. THE SCAB(DEHYDRATED EXUDATE AND DYING DERMIS) IS A PHYSICAL BARRIER TO HEALING THE DELAY BECAUSE EPIDERMAL CELLS CANNOT MOVE EASILY UNDER THE SCAB THERE MAY BE POOR COSMETIC RESULTS AND SCARRING. 2. EXPOSURE TO AIR REDUCES SURFACE TEMPERATURE OF THE WOUND AND DRIES THE WOUND CAUSING FURTHER DELAYS HEALING 3. GAUZE PACKING IMPAIRES THE QUALITY OF HEALING 4. THE DRESSING MAY ADHERE TO THE WOUND AND CAUSE TRAUMA WHEN IT IS REMOVED. FORMATION OF THE SCAB & THE RATE OF EPITHELIZATION OF SUPERFICIAL WOUNDS IN THE SKIN OF YOUNG DOMESTIC PIGS "THE DEMONSTRATION THAT A SIMPLE CHANGE IN PHYSICAL CONDITIONS AT THE WOUND SURFACE CAN HAVE SUCH A MARKED EFFECT ON THE RATE OF EPITHELIZATION,HAS AN IMPORTANT BEARING ON EXPERIMENTAL METHODS IN WOUND HEALING" EPITHELIZATION Under Normal(Dry) and Experimental(Moist) Conditions TIME -WOUND LENGTH EPIDERMIS (mm x 10-2) WINTER 1962 LENGTH SECTION (mm x 10-2) % EPIDERMIS DRY WOUNDS 1 DAYS 1 1,608 71, DAYS 7 26,212 77, DAYS 3 55,524 77, DAYS 9 77,902 78, Also at 9 and 11 days 100 MOIST WOUNDS 1 DAY 2 11,327 66, DAYS 8 77,598 78, DAYS 4 71,721 71, Also at 7,9 and 11 days 100 MOIST WOUND MANAGEMENT HINMAN C.D et AL Nature 26/10/63 EFFECT OF AIR EXPOSURE AND OCCLUSION ON EXPERIMENTAL HUMAN SKIN WOUNDS "MOST OCCLUDED SPECIMENS SHOWED SO MUCH MORE EPITHELIZATION THAN THE AIR-EXPOSED WOUNDS THAT THE DIFFERENCE WAS OBVIOUS WITHOUT BENEFIT OF MEASUREMENT" "EXPERIMENTAL SPLIT SKIN WOUNDS IN HUMAN VOLUNTEERS,RE-EPITHELIZATION WAS MORE RAPID IN THE OCCLUDED THAN IN THE AIR-EXPOSED CONTROL." EPITHELIZATION DAY SUBJECT WOUND No and GROUP TOTAL LENGTH SECTION TOTAL NEW EPIDERMIS % NEW GROWTH 3 DAYS A 51 E* 17,599 2, O# 5,693 1, B 53 E 22,656 2, O 12,411 5, C 116 E 8,902 1, O 6,639 1, D 120 E 7,960 1, O 1,942 1, DAYS E E 3,509 1, O 3,746 1, C 118 E 5, O 2,551 1, D E 2, O 2,730 1, [mmx10-2] [mmx10-2] *,CONTROL AIR EXPOSED #,OCCLUDED HINMAN

3 Wound Management Aims Maintain moist wound environment Control exudate and debris -moisture management (absorb/donate) -facilitate autolytic debridement -physically/chemically debride Maintain/improve circulation Insulate and protect Wound Bed Preparation Debridement Bacterial Balance Exudate Management? 3

4 Edge of wound TIME acronym Tissue Moisture imbalance Inflammation Infection Developed by the International Advisory Board on Wound Bed Preparation, 2002/3 Goal to describe the observable characteristics of chronic wounds within the framework of the scientific basis of Wound Bed Preparation Schultz GS, Sibbald RG, Falanga V, et al. Wound bed preparation: a systematic approach to wound management. Wound Repair and Regeneration 2003; 11:1 28 Biofilms impacted both T & I components Negative Pressure Wound Therapy (NPWT) impacted T I and M components New topical dressings impacted I component silver new antiseptic dressings -PHMB DNA-based identification of bacteria impacted I Diagnostics for proteases impacted E Major Developments last 10 years What has changed? Reintroduction of traditional non-surgical debridement methods (i.e. larval, enzymatic) New debridement methods (i.e. hydrosurgery, ultrasound) NPWT in combination with debridement and instillation of antiseptic solutions T: Tissue IWII Curriculum E+08 1.E+07 1.E+06 1.E+05 1.E+04 1.E+03 1.E+02 1.E+01 1.E+00 CFU / 5mm Biopsy Pseudomonas aeruginosa PA01 SA35556 Staphylococcus aureus Larval Debridement Therapy Before treatment Before treatment After 24hr treatment L. Cowan, J. Stechmiller, P. Phillips, Q.P. Yang and G. Schultz. Chronic Wounds, Biofilms and Use of Medicinal Larvae, Ulcers, Article ID , 7 pages;

5 What has changed? I: Infection & Inflammation What has changed? E: Edge Greater understanding of the different effects of antibiotics on planktonic and biofilm bacteria in wounds New developments in our understanding of how antimicrobial agents work (i.e. PHMB, iodine, honey, silver-containing dressings) Tobramycin rapidly kills planktonic Pseudomonas aeruginosa ( ) very effectively, but is not effective against biofilm Pseudomonas ( ). Costerton, Sci Am, 2001 The importance of accurate wound measurement is critical in relation to the other clinical actions of TIME E should also represent evaluation, using assessment tools and adjunctive therapies If E also represents evaluation Expanding: TIME Then we should expand our focus outwards from the wound to consider the wellbeing and quality of life of the patient The TIME acronym should not just focus on the wound bed A more holistic approach is needed TIME should be considered in relation to the patient, healing and therapeutic services environments TIME: expanding Patient the environment focus Epithelial edge Extending TIME Holistically Tissue debridement Wound bed preparation Moisture balance Inflammation Infection Surrounding skin Therapeutic services environment Cost benefit & QoL issues Holistic & systemic evaluation Healing environment D. Leaper and D. Smith Wound Needs Wound Needs 5

6 Cardiovascular Decreased vascular elasticity Coronary blood flow and cardiac output Peripheral vascular resistance Gastrointestinal Protein synthesis by liver Teeth, saliva taste sensation Gut innervation & peristalsis Blood is less efficiently pumped around the body therefore possible problems of oxygen supply to tissues Protein metabolism may cause protein deficiencies, no enjoyment in eating, all food tastes the same, ability to digest is slow so often they complain of always feeling full and so not interested in food. Genitourinary Nephrons and renal blood flow Bladder strength and capacity Glomerular filtration rate Continence issues, so they do not want to drink as much fluid as we would like and regularly suffer from bladder/renal infections, which make them very unwell and at risk of other problems. Also when incontinent urine may contaminate lower leg dressings. Pulmonary Elasticity of lungs and chest wall Alveoli, capillaries, cilia Vital capacity Poor lung capacity means they may have poor oxygen supply to the tissues and thus wound. Musculoskeletal Muscle power and coordination Erosion and ossification of joints Thinner muscle fibres Nervous Vision and hearing acuity Skeletal reflex time & pain threshold Neural control of circulation and velocity of nerve impulse conduction Decreased strength means less energy, lack of exercise means poorer oxygenation of tissues and again possibly the wound. With these changes 6

7 Immunologic Delayed hypersensitivity reaction T-cell and antibody responses Autoantibodies This means the elderly patient is at more risk of infection, but also more prone to sensitivities. Factors What influences wound healing in a negative way? Intrinsic Factors Affecting Healing HEALTH STATUS Circulation :- Arterial & Venous Anaemia IMMUNE FUNCTION Normal Immune Function help cleansing the wound CO-MORBIDITIES Diabetes, RA & other Diseases will impact on wound Healing Intrinsic Factors Affecting Healing AGE FACTORS Skin changes with Age Loss of Hair Follicles, Blood Supply Fragility, Loss of Sebaceous Glands, Receptors Skin become dry, Tissue-paper thin Intrinsic Factors Affecting Healing NUTRITIONAL STATUS Balanced diet Protein {Arginine}, Carbohydrates, Fats, Fluid Essential :- Vitamins A,B, K and C Minerals :- Iron, Copper and Zinc Extrinsic Factors Affecting Healing MECHANICAL STRESS Pressure Friction Shearing Forces 7

8 Extrinsic Factors Affecting Healing DEBRIS Slough, Necrotic Tissue, Eschar, Scab, Dressing Residue, Sutures Extrinsic Factors Affecting Healing DESICCATION If the wound Surface dries the Surface cells die MACERATION Excess Moisture will retard Healing and damage periskin TEMPERATURE The Body needs about 37 o Typical Leg Ulcer Note Maceration to the peri-skin Extrinsic Factors Affecting Healing INFECTION Will Retard Healing CHEMICAL STRESS Topical Agents may have a -ve effect on the wound and Cells e.g. Antiseptics OTHER FACTORS Smoking Radio-therapy Alcohol Drugs Typical Infected Leg Ulcer Note Erythema Drugs and Wound Healing Negative effects Prednisolone and other steroids Oral/systemic steroids Topical steroids NSAIDs Antibiotics (topical) Anti-neoplastics Hydroxyurea Positive effects Haemorrheologics (Pentoxifylline) Retinoids Phenytoin Antibiotics (Oral/systemic) 8

9 Drugs with a negative effect on wound healing - Corticosteroids Drugs in this class include prednisolone, prednisone, hydrocortisone, etc Inhibit nearly every aspect of wound healing! Inhibit acute wound healing only when given prior to or immediately after injury Due to inhibition of inflammatory phase Inhibit initial increase in vascular permeability and vasodilation (normal post trauma) due to inhibition of prostaglandin synthesis Drugs with a negative effect on wound healing - Corticosteroids Chronic wounds During inflammatory phase - macrophages Affects chemotaxis and proliferation of fibroblasts collagen production, inhibition of angiogenesis Reduce wound contraction during proliferative phase due to effects on fibroblasts Inhibit epithelial migration, poor quality tissue Decreased tensile strength of healed tissue in maturation phase Drugs with a negative effect on wound healing - Corticosteroids Chronic wounds Immune system effects (immunosppressive) susceptibility to infection chemotaxis and proliferation of T lymphocytes protein synthesis (modulation of gene transcription) - TGF-ß (cytokine involved with broad range of wound repair activities) Complex and detailed events more details in: Roberts, A. and Sporn, M. Transforming Growth Factor- ß in Clark, R. (Ed), The Molecular and Cellular Biology of Wound Repair, (2 nd edition), Plenum Press, New York, 1996 Drugs with a negative effect on wound healing - Corticosteroids Topically applied steroids used to treat Eczema or other dermatologic conditions Will cause vascoconstriction at the edge of a Wound if inadvertently applied. Caution should be used to separate the wound edge from the product used to treat the skin rash. Drugs with a negative effect on wound healing Antineoplastic drugs General points about antineoplastics Cytotoxic - not cancer cell-specific Range of classes and pharmacological actions generally exert effect on rapidly replicating cells ire cancer cells Wound cells may be replicating more rapidly than normal cells and so at risk Risk of extravasation injury Haematological changes may affect healing Drugs with a negative effect on wound healing Antineoplastic drugs Specific points about antineoplastics Haematological changes may affect healing Impact Red Blood Cells ( most) Impact White Blood Cells ( most) Myelosupression ( most) Neurotoxic (cis-platinum, Vinblastine, Vincristine, Carboplatin, Vindesine, Hexamethylamine) 9

10 Drugs with a negative effect on wound healing Antineoplastic drugs Hydroxyurea (Hydrea ) Non-nucleoside anti-metabolite Associated with causation of ulcers, esp malleolar, with long term use or high doses Lichenoid eruptions called hydroxyurea dermopathy after long periods of therapy Damage basal keratinocytes leading to dermal atrophy Platelet mediated inflammatory response leading to micro-thrombi formation Tobacco - a major cause of death Tobacco causes more illness and death than any other drug. In the financial year , 14,900 people died from smoking related diseases; around 89% of all drug caused deaths. Research estimates that one in two lifetime smokers will die from a disease caused by their smoking. Every year around 3,940 Victorians die from diseases caused by smoking Smoking Cigarettes are not the simple mixtures of tobacco leaves they appear to be. They are in fact very complex products containing an estimated 4000 chemicals. 43 carcinogens have been identified in tobacco smoke. Some of the major chemicals in cigarette smoke include Tar Nicotine Carbon Monoxide Hydrogen Peroxide Metals (eg. nickel, arsenic and cadmium) Radioactive compounds Agricultural chemicals and additives Smoking What is less well understood is the effect of smoking on wound healing. It was Mosley and Finseth in 1977 who concluded in their published study that cigarette smoking impairs Digital blood flow and wound healing. Mosley LH, Finseth F. Cigarette smoking:impairment of digital blood flow and wound healing in the hand. HAND 1977;9: Smoking The following year Mosley,Finseth &Goody showed, in an experimental animal model, that Nicotine systemically administered impairs Wound Healing. Since then a number of papers have been published demonstrating the negative effects on wound healing of cigarette smoking. Nicotine is a cutaneous vasoconstrictor this action is achieved by the release of adrenal and peripheral catecholamines, which also increases heart rate, blood pressure and oxygen demand. Nicotine also increases platelet adhesiveness increasing the risk of micro-vascular occlusion and tissue ischemia 10

11 As a result of this reduced blood flow there is a reduction in the flow of nutrients to the wound and a lower oxygen level. Nicotine will diminish red blood cells, fibroblast and macrophages. The red blood cells are essential in the transport of oxygen to the tissues via hemoglobin. The macrophages are involved in phagocytosis of the wound by removing bacteria that have the potential of resultant infection in the wound. Nicotine from smoking reaches the brain and muscle tissue soon after being inhaled resulting in: Increased heart rate (Pulse) Increased blood pressure and slowing of circulation in smaller vessels. Combined with vasoconstriction lowers skin temperature Nicotine can both relax skeletal muscles and increase muscle tension eg. Increase hand tremor after smoking Nicotine stomach secretions & changes brain activity Carbon monoxide has an affinity for haemoglobin 200 times that of oxygen. This will have a major effect in decreasing the oxygen-carrying capacity of the hemoglobin subsequently reducing the amount of oxygen available to the tissues. The combination of carbon monoxide and hemoglobin result in carboxyhemoglobin instead of oxy-hemoglobin. It will also lead to cellular hypoxia and impact on wound healing. The lack of oxygen will then contribute to the lack of collagen deposition, as oxygen is essential for the hydroxylation of proline. to ultimately produce collagen. Carbon Monoxide is quickly absorbed into the Blood reducing the capacity to carry oxygen. Passive smoking has the same effect. This results in a need for more effort to achieve the same physical result as in non-smokers, The heart must work harder for the same effect, especially when doing rigorous exercise. Studies have shown levels of CO in the blood of a 20 a day smoker can impair vision, perception of time and coordination. Hydrogen cyanide inhibits enzyme-systems necessary for oxygen transport at the cellular level. as well as oxidative metabolism. Once again the additive affect on the transport of oxygen to the tissue as with carbon monoxide will impact on wound healing. Without the availability of adequate amounts of oxygen cellular hypoxia will occur impacting of the ability of tissue to heal. 11

12 Drugs with a negative effect on wound healing Nicotine- Direct effects A study by Roseby Royal Children s Hospital Melbourne examined the effects of one cigarette on a group of young smokers who had not smoked for 12 hours. The tests studied pre and post one cigarette were: Blood Pressure, Lung Function, Carbon Monoxide in the Lungs, Laser Doppler arterial circulation, Muscle Tension Hand Tremor Error Drugs with a negative effect on wound healing Nicotine- Direct effects Test Area Pre-Smoking Post-Smoking Blood Pressure 110/70 135/85 Lung Function Normal Abnormal Carbon Monoxide in the Lungs 1 PPM 16 PPM Laser Doppler arterial circulation Muscle Tension Hand Tremor Error % 14.37% Roseby Royal Children s Hospital Melbourne Roseby Royal Children s Hospital Melbourne Conclusion Smoking and Tissue are incompatible Smoking is one of the major factors for non-healing wounds. I know it is not always simple however it is Essential that your patients be encouraged to quit smoking it will require an extreme Effort on all parties But it is worth it in the end Drugs with a negative effect on wound healing - Anti-platelet drugs Class includes Aspirin and other NSAIDs Inhibits inflammatory response and acid mucopolysaccharide synthesis in wounds Inhibit inflammatory mediators derived from arachidonic acid metabolism and platelet aggregation Inhibition of Cox-1 by NSAIDS could increase the local ischaemia and hypoxia associated with chronic venous ulcers Abd-El-Aleem et al 2001 Drugs with a negative effect on wound healing - Anti-platelet drugs Impact of COX-II inhibitors is unclear Reduction of scar formation Wilgus et al 2003 without disrupting epithelialization Delay gastric ulcer healing Baatar et al 2001 Reduced Ligament repair and strength in surgically incised medial collateral ligament in 50 SD rats half treated post op with a Cox-2 inhibitor when compared with the non-treated rats a 32% lower load to failure. Elder et al Delayed re-epithelialization in the early phase of wound healing Inhibition of angiogenesis Futagami et al 2002 Drugs with a negative effect on Wound Healing Anti-coagulants These Drugs are used to reduce blood viscosity and include Warfarin and Heparin. They inhibit proper coagulation and can adversely affect wounds by increasing the risk of haematomas and seroma formation. They can cause tissue necrosis purple toe syndrome There is some evidence of risk in terms of wound healing. 12

13 Sometimes we don t get what we expect 13