Goals Principles in wounds healing Nutrition, the Often Forgotten - PowerPoint PPT Presentation

4/16/2016 Goals • Principles in wounds healing Nutrition, the Often Forgotten Part of the Equation for Wound Healing • Critical Nutrients • Role of omega-3 fatty acids Marlene Grenon, MD Associate Professor of Surgery University of California San Francisco UCSF Vascular Surgery Symposium 2016 Nutritional Risk Factors for Impaired Chronic Wounds Wound Healing • Chronic Wounds: Wounds taking >4-6 weeks • Significant weight loss to heal • Inadequate protein intake • Types – Pressure ulcers • Inadequate nutrient intake – Post-op wounds • Extreme Body Mass index (low or high) with – Ulcers (venous, arterial) limited mobility – Burns • Hypoalbuminemia – Stomas • Dehydration – Amputation wounds Dorner et al, Adv Skin Wound Care 2009 Dorner et al, Adv Skin Wound Care 2009 1

4/16/2016 Malnutrition Renal impairment (albumin < 3.5mg/dl) (eGFR <60 ml/min) Wound Healing 27% 31% HR=3.77 HR=2.72 17% HR=6.7 -wound exudation 9% -fibrin clot HR=9.08 -neutrophils -epithelialization 15% 18% -macrophages -angiogenesis HR=5.65 HR=4.10 -collagen maturation -fibroblast proliferation -tensile strength -collagen cross-linking Hazard Ratios -wound contraction for Death 37% HR=4.54 Inflammation Owens CD et al (hsCRP> 5mg/L ) J Vasc Surg 2012 American Dietetic Association’s Wound Healing Nutrition Care Process • Medical Nutrition • Recommended Protein Vitamin C Glucosamine Therapy: assessments: Vitamin A Protein ZInc – Nutrition assessment – Anthropometric – Nutrition diagnosis measurements – Biochemical data – Nutrition intervention – Nutrition monitoring and (anemias) – Hydration status evaluation – Nutrition-focused clinical examination – Diet history American Dietetic Association 2009 2

4/16/2016 Water • Aid in hydration of wound sites and oxygen perfusion • Epithelial cells require moisture to migrate from the wound edge to close the wound • Act as a solvent for minerals, vitamins, amino acids, Critical Nutrients glucose • Transporting vital materials to cells and removing waste products Energy Role of Proteins -Sources: carbohydrates and fat • Maintenance and repair -Wound energy demand: collagen synthesis • Daily intake of 1- - Requirements 30-35 kcal/kg but need to be individualized of body tissue 1.5g/kg/day – Collagen synthesis Fats • Up to 3g/kg/day in Carbohydrates • Good source of energy (9cal/g) – Fibroblast proliferation • Stimulate insulin production and spares protein for wound severe wounds + release – Tissue remodeling healing • • Protein deficiency • Prevent gluconeogenesis Carries Vitamins A, D, E, K – Wound contraction • • Inadequate supplies Aids in absorption of Vit A – Poor wound healing impairs all stages of • – Maintain oncotic Provides padding under body • Caution with diabetes wound healing prominence and insulation of the required pressure skin • • Sources: wholegrain cereals, – Skin structure Overall: breads, potatoes, rice, pasta, – Underweight: gain weight biscuits – Overweight: weight maintenance Red and white meats, fish, eggs, liver, dairy products (milk, cheese • Sources: meat, full-fat dairy, oils yogurt), soy beans, legumes, seeds, nuts and grains Williams JZ, Surg Clin N Am 2003; Ord H. Br J Nurs 2007; Hurd TA, Wound Care 2004; Ord H Br J Nurs 2007 Edmonds J. Br J Community Nurs 2007 3

4/16/2016 Amino Acids- L-Arginine Albumin • Average dietary intake • Essential structural • Albumin and pre- • Although reflective of provides 4g/day protein synthesis and malnutrition, affected by • 9 g/day promotes wound albumin are a strong protein metabolism other conditions – Decrease muscle loss healing for pressure prognostic indicator and • hydration status • Nitric oxide pathway ulcers * level of morbidity in • • Source: proteins metabolism – Collagen deposition in many populations • • Side-effects: diarrhea. infection wound healing – Albumin half-life almost • • Enhance immune stress • 21 days liver disease function • • Improve secretion of – Pre-albumin 3 days renal disease • inflammation growth hormone and insulin Normal range: 3.4-5.4 g/dL Supplementation: Arginine 9g, Vit C (500 mg), zinc (30 mg) *Desneves KJ, Clin Nutr 2005 Vitamin A Vitamin C • Increases the • If deficient, • Important in collagen • If deficient, inflammatory response recommended dose: synthesis + crosslinking recommended dose: in wounds 10,000-25,000 IU x 7-10 • Angiogenesis 250-1000mg daily • Stimulates collagen days • Sources: fruit and • Immune system • Sources: milk, cheese, synthesis and cross- vegetables (oranges, • Increases absorption of linking eggs, fish dark green grapefruit, tomatoes, • Restore wound healing vegetables, oranges, red iron leafy vegetables) fruits, vegetables. • Deficiency increases the impaired by long-term • Side effects: diarrhea, steroid therapy or risk of wound infection diabetes scurvy – Mechanisms unclear Langemo D. Adv Skin Wound Care 2006; Ord H. Br J Nurs 2007. 4

4/16/2016 Zinc and Iron Nutrition and Wound healing in PAD Zinc Iron • Protein and collagen • Required in collagen synthesis, tissue growth and production and wound healing strength • Recommended intake for • Recommended intake in the non-healing pressure ulcers, general population: 15-50mg/day (no more than 8mg/day (18mg/day for 14 days as it can also menstruating females) • Sources: red meat, fish, interfere with wound healing) eggs, wholemeal bread, • Sources: red meat, fish and dark green leafy vegetables, shellfish, milk, poultry, eggs. dried fruits, nuts. • Side-effects: GI complaints • Side-effects: nausea and constipation -double-blinded fashion -270 subjects -arginine, glutamine and b-hydroxy-b-methylbutyrate or a control drink -16 weeks ->wound closure and time to complete healing FIGURE 3 Median wound area (cm 2 ) by week; arginine, glutamine and b-hydroxy-b-methylbutyrate supplementation (& ) (n = 129) and Control (s ) (n = 141). 5

4/16/2016 Nutrient recommendations CVD Low PAD albumin subgroup subgroup FIGURE 4 Cumulative probability of wound closure vs. albumin at FIGURE 5 Cumulativeprobability of wound closure vs. ankle– entry by patient subgroups. Each point (x, y) represents the proportion, brachial index at entry by patient. Each point (x, y) represents the y, of subjects with total wound closure in the subgroup of subjects proportion, y, of subjects with total wound closure in thesubgroup of with baseline albumin ≤ x. S pecifically, for the subgroup of subjects subjects with baseline ankle–brachial index ≤ x. S pecifically, for the (N = 127) with albumin ≤ 40 g/l, proportion healed is higher in the subgroup of subjects (N = 119) with ankle–brachial index < 1.0, arginine, glutamine and b-hydroxy-b-methylbutyrate supplementation proportion healed is higher in thearginine, glutamine and b-hydroxy- b-methylbutyrate supplementation group (& ) (n = 58) vs. the group (& ) (n = 61) vs. thecontrol (s ) (n = 66) (P = 0.0325) Cochran– Nosova, JVS 2015 M antel–Haenszel test stratified by site. control group (s ) (n = 61) (P = 0.0079) CM H test stratified by site. OMEGA Studies + SPMs Studies Inflammation and Resolution Total: >200 patients OMEGA- Cross- sectional To start recruitment OMEGA- OMEGA- SPM PAD I Completed (n=80) OMEGA STUDIES To start recruitment OMEGA OMEGA- EVAR PAD II Failure of resolution contributing to chronic inflammation OMEGA- PVI Recruiting (20/70) Recruiting (8/30) Serhan CN, Chiang N. Curr Op Pharm 2013 6

4/16/2016 Specialized Pro-Resolving Lipid Mediators ω -6 fatty acid ω -3 fatty acid Arachidonic acid Eicosapentaenoic acid Docosahexaenoic acid AA EPA DHA 12-LOX or COX-1 15-LOX 15-LOX 15-LOX typeI 5-LOX 18-HEPE COX-2 TXA 2 14-HpDHA 17(S)-HDHA 17-HpDHA PGE 2 Thromboxane 5-LOX Prostaglandins LTB 4 14-HDHA Leukotrienes LXA 4 RvE1 RvE2 (N)PD1 RvD1-RvD4 MaR1 LXB 4 Lipoxins E-series Protectins Maresins D-series Resolvins Resolvins RvD1 RvD2 OMEGA-PAD I Trial: 4.4g fish oil/day in PAD Grenon et al, JAHA 2015 7

4/16/2016 Summary • Assessment, diagnosis, intervention and evaluation – Perform nutritional assessment (weight, pre-albumin level and serum albumin level) – Encourage dietary intake or supplementation – Give vitamin and mineral supplements if deficiencies are confirmed or suspected • Dietary consultation • Await further trials and evidence – Promising compounds 8