Date: 07/04/2014 Our ref: I write in response to your request for information in relation to use of biotherapy treatments in NHS Lothian.

Transcription

1 Lothian NHS Board Waverley Gate 2-4 Waterloo Place Edinburgh EH1 3EG Telephone Fax Date: 07/04/2014 Our ref: 4371 Enquiries to: Bryony Pillath Extension: Direct Line: Dear FREEDOM OF INFORMATION BIOTHERAPY TREATMENTS I write in response to your request for information in relation to use of biotherapy treatments in NHS Lothian. I have been provided with information to help answer your request by Ruth Ropper, Tissue Viability Lead Nurse, and the Pharmacy Directorate, NHS Lothian. Question: 1. Does your health board treat patients using maggot therapy (biotherapy)? Answer: Yes, both free range and bagged varieties are used. Question: 1a. When did you first start using maggots? Answer: Free range maggots have been used in NHS Lothian since 15 May Bagged maggots have been used since they were first produced in the year Question: 1b. What conditions are maggots used to treat? Answer: Maggots are used for debridement of sloughy wounds such as pressure ulcers, leg ulcers, dehisced surgical wounds, diabetic foot ulcers and haematomas. Question: 1c. Please provide procedural guidelines given to staff in relation to using this form of treatment. Headquarters Waverley Gate, 2-4 Waterloo Place, Edinburgh EH1 3EG Chair Brian Houston Chief Executive Tim Davison Lothian NHS Board is the common name of Lothian Health Board

2 4371 Biotherapy March 2014 Answer: I have enclosed with this response guidance from BioMonde, the company who supply medical maggots. This guidance is available to NHS Lothian staff via the internal Intranet Tissue Viability site and includes the following documents: - Larval Debridement Therapy: BioBag application guide and daily care - Larval Debridement Therapy: Boot/Sleeve Net application guide and daily care - Larval Debridement Therapy: Flat Net application guide and daily care - All Wales Guidance for the Use of Larval Debridement Therapy - Larvae Management Poster - Larval Therapy Patients and Carers Guide - BioBag Product Sizes and Codes - Larval Debridement Therapy: an economic, scientific and clinical evaluation Question: 1d. How many maggots have been used since they were first introduced - broken down by year. 1e. How much has been spent on buying maggots and where are they bought from? Answer: I am advised that this data is not collected centrally. There are many years of data which have been collected separately for different sites and are not collected in a way that is comparable. This means we are not able to give accurate data to answer your questions. Since they were introduced, maggots have been bought in various forms including pots of free-range larvae and maggot bags of different sizes. If you would like any more specific information about spend and amounts of these products purchased please specify this and we will try to answer this for you. NHS Lothian currently purchases medicinal maggots from the company BioMonde, previously Zoobiotic. Question: 2. Does your health board treat patients using leeches? Answer: Yes, NHS Lothian uses leeches for treatment. Question: 2a. When did you first start using leeches? Answer: Page 2 of 5

3 4371 Biotherapy March 2014 Leeches have been used in NHS Lothian since 17 July Question: 2b. What conditions leeches used to treat? Answer: Leeches are used primarily in plastic surgery for management of congested flaps and digits which have been re-implanted. Question: 2c. Please provide procedural guidelines given to staff in relation to using this form of treatment. Answer: I have enclosed Standard Operating Procedures for pharmacy and guidance for ward staff regarding the use of leeches, including the following documents: - Procedure to Order and Receive Medicinal Leeches; - Procedure to Supply Leeches to Wards; - Procedure to Make Up a Leech Pack; - Guidelines for Leech Care; - Leeches Information Leaflet. Question: 2d. How many leeches have been used since they were first introduced - broken down by year. 2e. How much has been spent on buying leeches and where are they bought from? Answer: I am advised that this data is not collected centrally. There are many years of data which have been collected separately for different sites and are not collected in a way that is comparable. This means we are not able to give accurate data to answer your questions. If you would like any more specific information about spend and amounts of these products purchased please specify this and we will try to answer this for you. NHS Lothian currently purchases medicinal leeches from the company BioPharm. Question: 3. Does your health board treat patients using honey? Page 3 of 5

4 4371 Biotherapy March 2014 Answer: Yes, NHS Lothian uses honey for treatment. Question: 3a. When did you first start using honey? Answer: Honey has been used for treatment in NHS Lothian since 5 th Jan 2007; Question: 3b. What conditions do you treat with honey and what variety of honey is used? Answer: Honey is used to treat sloughy, necrotic and infected wounds of all types, for example pressure ulcers, dehisced surgical wounds and diabetic foot ulcers. It is also used to treat some hard to heal wounds as Manuka honey has properties which stimulate cells required for wound healing. The honey used is medical grade Manuka (Leptospermum) honey from New Zealand, which has been gamma irradiated to ensure that it is safe for use on open wounds. It is supplied either in the form of 100% pure honey in a tune or carrier such as a tulle, or in an alginate dressing. A light version which uses Manuka oil and less honey is also used to ensure the antibacterial effect of the honey dressing is maintained. Question: 3c. Please provide procedural guidelines given to staff in relation to using this form of treatment. Answer: Guidance for staff is given in the Lothian Joint Formulary which can be found on the intranet at the following web address: management%20products/(k)/pages/default.aspx A copy of this and other guidance available to staff is also enclosed with this response, along with a patient information available from the current NHS Scotland contracted supplier. Question: 3d. How much honey has been used ie jars?, since it was first introduced - broken down by year. Page 4 of 5

5 4371 Biotherapy March e. How much has been spent on buying the honey and where is it bought from? Answer: I am advised that this data is not collected centrally. There are many years of data which have been collected separately for different sites and are not collected in a way that is comparable. This means we are not able to give accurate data to answer your questions. Honey comes in a variety of dressing formats which contain Manuka honey in the Lothian Joint Formulary and these are used more frequently than the honey in tubes. If you would like any more specific information about spend and amounts of these products purchased please specify this and we will try to answer this for you. NHS Lothian currently purchases honey tubes from the company AAH Pharmaceuticals. I hope the information provided helps with your request. If you are unhappy with our response to your request, you do have the right to request us to review it. Your request should be made within 40 working days of receipt of this letter, and we will reply within 20 working days of receipt. If our decision is unchanged following a review and you remain dissatisfied with this, you then have the right to make a formal complaint to the Scottish Information Commissioner. If you require a review of our decision to be carried out, please write to the FOI Reviewer at the address at the head of this letter. The review will be undertaken by a Reviewer who was not involved in the original decision-making process. FOI responses (subject to redaction of personal information) may appear on NHS Lothian s Freedom of Information website at: Yours sincerely ALAN BOYTER Director of Human Resources and Organisational Development Cc: Chief Executive Page 5 of 5

6 Larvae application guide (BioBag) Fig.1 Apply barrier cream/bandage Fig.3 Place a moistened gauze swab over the BioBag dressing Larval Debridement Therapy Skin Wound Barrier Absorbent pad Application guide and daily care Fig.2 Apply the BioBag dressing Fig.4 Secure the dressing BioBag BioBag dressing Daily care Daily change of the secondary dressings where possible is recommended and when strikethrough is present Avoid sustained, direct pressure as this may occlude the larvae. Short periods for the purposes of mobilisation are permissible Check larvae are viable at secondary dressing changes movement of larvae and presence of dark red exudate indicate the larvae are alive Re-apply barrier where necessary to the periwound area Ensure damp gauze is replaced on top of the BioBag at each secondary dressing change Ensure that all outer/secondary dressings are not occlusive and are permeable to the air After 72 hours, reassess wound to decide on further treatment. If a further NEW larval treatment is required, schedule a new order If debridement is near completion and no further NEW larval treament is required, plan follow on dressing treatment to be completed at end of day 4 On removal, double bag and treat as clinical waste in line with your local Grade A Clinical Waste Disposal Protocol Do not immerse in water. Do not occlude. Larvae (BioBag) 4 Day Treatment Cycle 0hrs 24hrs 48hrs 72hrs 96hrs Application of larvae Assess and reorder (if required) Daily Care Daily Care Daily Care Daily Care Repeat as required Remove and dispose 1. Materials required BioBag or combination of BioBag sizes, suitable for the wound size A wound dressing pack Barrier cream or Zinc paste to protect intact peri-wound skin (Sudocreme or other suitable) An absorbent (non-occlusive) dressing pad and a lightweight retention bandage Sterile saline for irrigation of wound or dressing residues & moistening the primary swab. 2. Preparation 1. Prepare the peri-wound area and wound bed, irrigate to remove residue and loose material 2. Protect intact skin around the margin of the wound by applying a thin layer of the barrier cream/bandage. (fig.1) 3. Applying larvae to the wound 1. Remove the BioBag from the transport vial 2. Place onto wound so that where possible the wound margin is covered. Fold/double back excess net of the bag away from peri-wound skin (fig.2) 3. Place a saline moistened gauze swab over the BioBag dressing (especially if it is a very dry wound) (fig.3) 4. Secure well with a secondary dressing to avoid slippage and to ensure surface contact of BioBag is maintained (fig.4) Ancillary dressings should be selected in order to manage exudates All outer dressings MUST be non-occlusive as the larvae need oxygen to survive Very wet outer dressings may occlude and suffocate the larvae. See overleaf for sizing guide and ordering information. BM197_01_0413/IP

7 BioBag sizes and codes BB x 10 cm BB x 4 cm BB100 5 x 4 cm Larvae (BioBag) 4 Day Treatment Cycle 0hrs 24hrs 48hrs 72hrs 96hrs Application of larvae Assess and reorder (if required) Daily Care Daily Care Daily Care Daily Care Repeat as required Remove and dispose Notes: BB200 5 x 6 cm BB x 6 cm Code Description BioBags BB50 2.5x4cm BB100 5x4cm BB200 5x6cm BB300 12x6cm BB400 10x10cm Ordering larvae Orders received by us before 2pm will qualify for inclusive next day delivery, or a future planned date of your choosing. Please allow time for your own internal procurement/pharmacy to process the order. Telephone: orders@biomonde.com Fax : Office Hours Monday to Friday 8:30am 5:00pm Storage Keep in transit containers Store at a temperature of 6 C to 25 C (products do not need to be refrigerated) Must be applied by expiry date, usually the day after delivery, for optimal results BioBag dressings can be left in place for up to 4 days See overleaf for application guide and daily care. For assistance outside working hours please call our Clinical Helpline:

8 Calculating how much larvae to order Larval Debridement Therapy Application guide and daily care 1. Measure the dimensions of the wound in centimetres 2. Pick the nearest size from the measurements on the left of the chart 3. Move sideways to the appropriate percentage of wound coverage 4. State the number of pots required from within the coloured cell. Note that the calculator only measures the surface of the wound. If the wound has significant depth, more larvae may be required. Maximum Percentage of wound covered with slough/necrotic tissue wound size (cm) 20% 40% 60% 80% 100% up to 2 x x x x x x x x x x x x Notes: Boot/Sleeve Net Daily care Applying/securing outer dressings Removal and disposal Ordering larvae Daily change of the outer secondary dressings is recommended and when strikethrough is present Avoid sustained, direct pressure as this may occlude the larvae. Short periods for the purposes of mobilisation are permissible Do not immerse in water, do not occlude At dressing changes, ensure the viability of the larvae by assessing their size, movement and the presence of dark exudates All outer dressings MUST be non-occlusive as the larvae need oxygen to survive Very wet outer dressings may occlude and suffocate the larvae. 1. Remove and bag outer dressings 2. Remove retention netting containing as many of the larvae as possible 3. Irrigate or wipe remaining larvae away from wound area into the Clinical Waste Bag 4. Double bag and treat as clinical waste in line with your local Grade A Clinical Waste Disposal Protocol. Orders received by us before 2pm will qualify for inclusive next day delivery, or a future planned date of your choosing. Please allow time for your own internal procurement/pharmacy to process the order for it to be received in time. Telephone: Resecure retention net or border if required to prevent loss of larvae Larvae (Boot/Flat Net) 3 Day Treatment Cycle orders@biomonde.com Fax : After 48 hours, reassess wound to decide on further treatment. If a further NEW larval treatment is required, schedule a new order If debridement is near completion and no further NEW larval treament is required, plan follow on dressing regime to be completed at end of day 3. 0hrs 24hrs 48hrs 72hrs Application of larvae Assess and reorder (if required) Daily Care Daily Care Daily Care Repeat as required Remove and dispose Office Hours Monday to Friday 8:30am 5:00pm For assistance outside working hours please call our Clinical Helpline: See overleaf for application guide. BM199_02_0413/IP

9 Larvae application guide (Boot/Sleeve) As closed boot dressing As a sleeve dressing fig.1 fig.3 fig.5 fig.8 Boot dressing Hydrocolloid dressing Skin Hydrocolloid dressing Hydrocolloid retention border Barrier cream Wound Wound fig.6 Invert the net onto the wound Trim closed end of boot fig.9 fig.2 Tape the net to the retention border fig.4 Hydrocolloid dressing Wound Net rolled back Wound Hydrocolloid dressing fig.7 Trim open end of boot 1. Preparation and materials 2. Using the retention net 3. Applying larvae to the wound Larvae pots (see sizing/selection guide) As a closed boot dressing ydrocolloid dressings for the creation of the H retention border This version of the retention net allows application of larvae to extremities and circumferential wounds. 1. C ut a selection of lengths of the Sleek tape suitable for initial fixing of the net wound cleansing pack or dressing pack, A sterile saline and scissors roll of waterproof plastic surgical adhesive A tape (Sleek or other equivalent) Sterile gauze or non-woven swabs n absorbent (non-occlusive) dressing pad and A lightweight retention bandage, adhesive tape. 1. P repare the peri-wound area and wound bed, irrigate to remove residue and loose material. 2. E nsure where possible the peri-wound area is clean and dry. 3. U sing strips of the Hydrocolloid (3-5cm wide) prepare the retention border (fig.1). 1. P rotect areas of intact peri-wound skin with a thin layer of barrier cream or pieces of bandage/swab impregnated with barrier cream. Take care that the cream does not block the net pores (fig.1) 2. T rim the open end of the boot retention net to allow comfortable fixation to the retention border with a minimum of excess (fig.2). As a sleeve dressing 1. B y trimming the closed end of the boot a sleeve can be formed (fig.3) 2. W hen creating a sleeve using Sleek tape, secure one end of the sleeve to the retention border then roll back away from the area (fig.4). 2. A dd about 5ml of sterile saline to the container of larvae and gently agitate to suspend them (fig.5) 3. I f more than one pot is being used, pour the contents of the first into the second and repeat gentle agitation 4. H olding the net, place a swab underneath and add few drops of saline onto the net (fig.6) 7. O nce larvae are on the wound and under the retention net, immediately secure the net to the retention border with precut waterproof (Sleek) tape (fig.9) 8. I t can be helpful to apply more tape to the edges of the first securing layer to give the best possible seal. Take care not to occlude the net, to allow the passage of air to the larvae. See overleaf for secondary dressing instructions and daily care 5. C arefully pour the larvae from the container onto the net (fig.7) ( It may be preferable to pour the larvae onto a swab and then gently wipe them onto the wound area) 6. Invert the net onto the wound (fig.8)

10 Calculating how much larvae to order Larval Debridement Therapy Application guide and daily care 1. Measure the dimensions of the wound in centimetres 2. Pick the nearest size from the measurements on the left of the chart 3. Move sideways to the appropriate percentage of wound coverage 4. State the number of pots required from within the coloured cell. Note that the calculator only measures the surface of the wound. If the wound has significant depth, more larvae may be required. Maximum Percentage of wound covered with slough/necrotic tissue wound size (cm) 20% 40% 60% 80% 100% up to 2 x x x x x x x x x x x x Notes: Flat Net Daily care Applying/securing outer dressings Removal and disposal Ordering larvae Daily change of the outer secondary dressings is recommended and when strikethrough is present Avoid sustained, direct pressure as this may occlude the larvae. Short periods for the purposes of mobilisation are permissible Do not immerse in water, do not occlude At dressing changes, ensure the viability of the larvae by assessing their size, movement and the presence of dark exudates All outer dressings MUST be non-occlusive as the larvae need oxygen to survive Very wet outer dressings may occlude and suffocate the larvae. 1. Remove and bag outer dressings 2. Remove retention netting containing as many of the larvae as possible 3. Irrigate or wipe remaining larvae away from wound area into the Clinical Waste Bag 4. Double bag and treat as clinical waste in line with your local Grade A Clinical Waste Disposal Protocol. Orders received by us before 2pm will qualify for inclusive next day delivery, or a future planned date of your choosing. Please allow time for your own internal procurement/pharmacy to process the order for it to be received in time. Telephone: Resecure retention net or border if required to prevent loss of larvae Larvae (Boot/Flat Net) 3 Day Treatment Cycle orders@biomonde.com Fax : After 48 hours, reassess wound to decide on further treatment. If a further NEW larval treatment is required, schedule a new order If debridement is near completion and no further NEW larval treament is required, plan follow on dressing regime to be completed at end of day 3. 0hrs 24hrs 48hrs 72hrs Application of larvae Assess and reorder (if required) Daily Care Daily Care Daily Care Repeat as required Remove and dispose Office Hours Monday to Friday 8:30am 5:00pm For assistance outside working hours please call our Clinical Helpline: See overleaf for application guide. BM198_02_0413/IP

11 Larvae application guide (Flat Net) fig.1 fig.3 fig.6 fig.8 Hydrocolloid dressing Invert the net onto the wound Wound fig.2 fig.4 fig.7 Cut the net to size Tape the net to the retention border fig.5 1. Materials required 2. Preparation Larvae pots (see sizing/selection guide) Creating a retention border 3. I f more than one pot is being used, pour the contents of the first into the second and repeat gentle agitation 4. Applying/securing outer dressings (fig.8) ydrocolloid dressings for the creation of the H retention border 1. P repare the peri-wound area and wound bed, irrigate to remove residue and loose material 4. H olding the net, place a swab underneath and add few drops of saline onto the net (fig.4) ll outer dressings MUST be non-occlusive as A the larvae need oxygen to survive wound cleansing pack or dressing pack, A sterile saline and scissors 2. E nsure where possible the peri-wound area is clean and dry 5. C arefully pour the larvae from the container onto the net (fig.5) ery wet outer dressings may occlude and V suffocate the larvae. roll of waterproof plastic surgical adhesive A tape (Sleek or other equivalent) 3. U sing strips of the Hydrocolloid (3-5cm wide) prepare the retention border (fig.1). Sterile gauze or non-woven swabs Cutting the net to size n absorbent (non-occlusive) dressing pad and A lightweight retention bandage, adhesive tape. 1. C ut the net to size so that it overlaps approximately half the width of the retention border (fig.2). 3. Applying larvae to the wound 1. C ut a selection of lengths of the Sleek tape suitable for initial fixing of the net 2. A dd about 5ml of sterile saline to the container of larvae and gently agitate to suspend them (fig.3). ( It may be preferable to pour the larvae onto a swab and then gently wipe them onto the wound area) See overleaf for daily care instructions. 6. Invert the net onto the wound (fig.6) 7. O nce larvae are on the wound and under the retention net, immediately secure the net to the retention border with precut waterproof (Sleek) tape (fig.7) 8. I t can be helpful to apply more tape to the edges of the first securing layer to give the best possible seal. Take care not to occlude the net, to allow the passage of air to the larvae.

12 All Wales Tissue Viability Nurse Forum Fforwm Nyrsys Hyfywedd Meinwe Cymru Gyfan All Wales Guidance for the use of: Larval Debridement Therapy Endorsed by

13 The All Wales Guidance for the Use of Larval Debridement Therapy (LDT) This guidance for the use of Larval Debridement Therapy has been written in collaboration with the All Wales Tissue Viability Nurse Forum and BioMonde. Guideline development group: On behalf of the All Wales Tissue Viability Nurse Forum: Julie Evans Tissue viability nurse, Abertawe Bro Morgannwg University Health Board Ceri Harris Clinical nurse specialist, Cardiff and Vale University Health Board Marilyn Jenkins Tissue viability nurse, Abertawe Bro Morgannwg University Health Board Karen Kembery Tissue viability nurse, Abertawe Bro Morgannwg University Health Board Rhian Parry-Ellis Tissue viability nurse, Betsi Cadwaladr University Health Board Denise Roberts Tissue viability specialist nurse, Betsi Cadwaladr University Health Board Jayne Warren Clinical nurse specialist, Aneurin Bevan Health Board On behalf of BioMonde : Jane Arnold National sales manager Kris Flinn European sales and marketing director Willi Jung Group director scientific affairs Ewan Murray European marketing manager Published by: Wounds UK, London. Web: All Wales Tissue Viability Nurse Forum The All Wales Tissue Viability Forum was formed in September 2003 and has the following aims that form part of the six key principles from the Institute of Medicine (Welsh Assembly Government, 2005): Safety, Effectiveness, Patient-centred, Timely, Efficient and Equitable 1. To raise awareness of tissue viability in order to improve patient outcomes 2. To raise awareness of the impact of tissue viability in health economics 3. To promote evidence-based practice in tissue viability and influence appropriate policy across Wales 4. To be recognised by the Welsh Assembly Government as a knowledgeable and valuable resource 5. To contribute to the body of knowledge by initiating and participating in tissue viability research and audit 6. To improve patient outcomes by maintaining the links with academia and disseminating knowledge relating to tissue viability to all healthcare providers 7. To work in partnership with industry in order to improve patient care 8. To provide peer support to all tissue viability nurses working in Wales.

14 Contents Page 1 Purpose 4 2 Introduction 4 3 What is debridement? 4 4 Mode of action 4 5 Indications for use 5 6 Cost-effectiveness 5 7 Patient assessment prior to use 5 8 Treatment pathway 7 9 Contraindications and associated risks 8 10 Interactions with other medicinal products 8 11 Choosing mode of application 9 12 Application options 9 13 Prescribing and ordering Step -by-step application intructions: BioBag Step-by-step application intructions: Free range larvae Looking after your larval therapy: management plan Removal and disposal Discharge guidance References Appendix 1: Frequently asked questions Appendix 2: Application guide and daily care 22 Guidelines for the use of Larval Debridement Therapy 1

15 1. Purpose The purpose of these guidelines is to provide knowledge for the appropriate use of larval debridement therapy and the management of patients receiving this therapy. The guideline is designed to support qualified healthcare professionals in managing wound debridement using larval therapy and to make sure it is carried out in a safe and clinically effective manner, acceptable to patients and carers. These guidelines aim to ensure the appropriate use of larval therapy within all Welsh NHS Trusts and Health Boards. These organisations are required to provide care services within commissioned services which meet these requirements, and to provide guidance for healthcare professionals to establish how suitable larval treatment is for each individual patient. It is suggested that this guidance should form part of tissue viability and infection prevention protocols. The guidance provided by this document is based on expert consensus which, along with audit, has been suggested as a positive method of directing care (Ousey et al, 2010). 2. Introduction There are, at present, no national guidelines available for the appropriate use of larval debridement therapy and the management of patients receiving this therapy. The National Institute for Health and Care Excellence (NICE, 2001) states that, to date, there is no robust evidence to support any particular method of debridement and recommends that health professionals consider biosurgical techniques (sterile maggots) as one method of debridement that may also reduce pain and be acceptable to patients (NICE, 2001). The choice of debriding agent should be based on impact on comfort, odour control and other aspects relevant to patient acceptability, type and location of wound and total cost. (NICE, 2001). 3. What is debridement? NICE describes debridement as the removal of devitalised or infected tissue, fibrin, or foreign material from a wound ( debris ). The body can remove these by natural processes, but large quantities of debris can delay healing and provide an environment for infection (NICE, 2001). Wound debridement is a component of wound bed preparation (Fletcher, 2005). Wound bed preparation involves producing an optimal healing environment by removing sloughy and necrotic tissue, managing wound exudate and restoring bacterial balance (Dowsett, 2002). There is consensus about the need for effective debridement among wound healing experts (EWMA, 2004; EWMA, 2013; Wounds UK, 2013). Debridement is considered to be a beneficial component of wound management due to the following factors: 1. Without debridement, a wound will never heal. Furthermore, surgical skin grafting, or other therapeutic methods supporting wound closure can only be applied after the wound is clean and well granulated (Schultz et al 2003) 2. There is an inherent risk of infection if wound debris is not removed as quickly as possible, as it harbours bacteria which may penetrate into the wound environment and cause local or systemic infections with the risk of sepsis 3. The presence of necrotic tissue may prevent a clinician from gaining an accurate picture of the extent of tissue destruction, thus inhibiting the clinician s ability to assess the wound correctly (Vowden and Vowden, 1999a; Leaper, 2002; Weir et al, 2007). Where surgical debridement is not an option and rapid removal of devitalised tissue is required, larval therapy is a recognised option (Boulton, 2007). Due to the essential role of debridement in wound management, it is important that the method of debridement selected is the most effective for the patient, and that this effectiveness is not limited by the skills of the practitioner (Gray et al, 2010). Selection of debridement methods should reflect the needs of the patient and be based on the knowledge and appropriate skills of the clinician, ensuring that every patient has access to the most appropriate method. 4. Mode of action The larvae of the greenbottle fly (Lucilia sericata) physically feed on dead tissue, cellular debris and serous drainage (exudate) present in sloughy wounds. It is their characteristic feeding action that physically breaks up the necrotic or sloughy tissue, which is then consumed and digested. The process involves the physical actions of the larvae and proteolytic enzymatic digestion. They feed mainly by a process of extracorporeal digestion. Secreting collagenases, trypsin-like and chymotrypsinlike enzymes which breakdown devitalised tissue into a semiliquid form which the larvae can ingest. The larvae of Lucilia sericata do not digest living human tissue. This selective process is one of the major advantages of larval debridement therapy as it spares the healthy tissues necessary for healing (Gottrup and 2 Guidelines for the use of Larval Debridement Therapy

16 Jørgensen, 2011). Larvae also have an antibacterial effect within the wound as bacteria contained in liquefied material is ingested and digested at the same time, thus reducing the bioburden within the wound. In addition, larval secretions can prevent the formation of, and reduce pre-formed, biofilms (Harris, 2009; Cazander et al, 2009). 5. Indications for use The application of larval therapy is an effective mode of debridement and may be applied and managed by any qualified healthcare practitioner who has reached an appropriate level of competency through training and who has adequate provision of clinical support. However, the decision and approval to administer larval therapy must be sought from an appropriate prescriber as per local policy (i.e. surgeon, medical team, tissue viability nurse/clinical nurse specialist, podiatrist, advanced nurse practitioner or non-medical prescriber such as district nurses). Larval therapy is indicated where an overall clinical decision has been made for the rapid debridement of devitalised tissue which is delaying wound healing. This will prepare the wound bed for products and treatments designed to enhance wound healing. 6. Cost-effectiveness A recent study by Professor Ceri Philips and the Swansea Centre for Health Economics at Swansea University, examining the clinical efficacy and cost-effectiveness of larval debridement therapy in wound debridement, concluded that larval therapy is cost-effective when compared with other mainstream debridement interventions, including surgical, sharp, mechanical and autolytic debridement. The cost of wound care is not simply determined by dressing cost, but is influenced by a multiplicity of factors. The factors that specifically impact on the cost-effectiveness of debridement include: Unit cost of treatment Length of treatment Number of procedures required Cost and likelihood of infection Cost and likelihood of adverse events. 7. Patient assessment prior to use Wound assessment prior to the application of larval debridement therapy should be carried out by a qualified healthcare professional according to local policy. Application and evaluation may be undertaken by a competent qualified healthcare professional who has received training on the management of patients receiving larval debridement therapy. Every healthcare professional is responsible for maintaining his or her competence. A holistic assessment should be undertaken and include the following: 1. A full assessment of the patient, wound type and wound bed. This should be undertaken and the results documented prior to larval debridement therapy, taking into account: a) Ability to offload pressure. b) Any results of vascular studies (see contraindications for use of larval debridement therapy) 2. Patient consent informed verbal consent should be obtained and documented where appropriate. 3. A patient s and carer guide should be provided for all patients. Table 1. The types of wounds for which larval debridement therapy may be used Diabetic ulcers Venous ulcers Arterial/ischaemic ulcers Mixed arterial venous ulcer Pressure ulcers Post traumatic wounds/ulcers, i.e. haematomas Necrotising fasciitis* post debridement Pilonidal sinus* post surgery Non healing surgical wound MRSA infected wound Figure 1. From eggs to debridement. Lifecycle of the fly Adapted from: Chan et al (2007) *See contraindications Guidelines for the use of Larval Debridement Therapy 3

17 Types of wound for which larval debridement may be used Heel pressure ulcer Before treatment After treatment (pictures with permission of Julie Evans) Sacral pressure ulcer Before treatment After treatment (pictures with permission of Alison Chandler) Lower limb haematoma Before treatment After treatment (pictures with permission of Jayne Warren) 4 Guidelines for the use of Larval Debridement Therapy

18 8. Treatment pathway: for the use of Larval Debridement Therapy Selection of moist sloughy/ necrotic wound Does the patient and wound meet the indications for usage? Yes Completion of wound assessment form Refer patient to competent Larval Debridement Therapy initiator, Tissue Viability Service or Podiatry to confirm suitability No Seek advice on other treatment options from the Tissue Viability Service or Podiatry Discuss treatment option with an authorised prescriber (medical/ surgical team/gp) and obtain approval especially if financial approval is required Discuss treatment option with patient, assess level of understanding/ concordance, level of mental capacity, obtain consent and document in medical or nursing notes Select appropriate application choice and order numbers (see calculator page 11) and obtain appropriate written treatment request, e.g. prescription/once only drug chart from authorised prescriber (e.g. doctor or independent prescriber) Ensure written instruction is despatched to the appropriate pharmacist or ordering centre before 2pm for delivery the next day if required, or on a selected date Ensure appropriate management plans and instructions are made available to all healthcare professionals who will be involved in the management of the larval debridement therapy Apply the BioBag or Free Range treatment in accordance with guidelines Manage treatment in line with guidelines, documenting progress and other associated physical indications (e.g. pain management) of the larval debridement therapy Assess debridement progress on the day prior to treatment completion to ascertain the need for further treatment applications and order as appropriate to avoid a gap in the treatment Remove and dispose of treatment in line with guidelines Guidelines for the use of Larval Debridement Therapy 5

19 9. Contraindications and associated risks Contraindications: Bagged or loose larvae must not be used on wounds that have a tendency to bleed or on wounds close to an exposed major blood vessel Complex wounds such as sinuses (known as fistulae) should be treated with caution in conjunction with medical supervision Bagged or loose larvae should not be used on wounds with dry necrotic eschar; rehydration is required in the first instance Bagged or loose larvae should not be used on a patient on anticoagulants where the relevant clotting marker is not within an acceptable clinical range Bagged or loose larvae should be used with caution on wounds over adjacent exposed organs or leading to a body cavity, and only under the close supervision of the doctor or nurse responsible for the patient Bagged or loose larvae can be used on suspected necrotising fascitis, but only once a thorough assessment has been carried out and surgical intervention rejected, or as an adjunct to surgery. Associated risks: There have been reports of increased pain at the wound site (particularly in wounds where pain is already present prior to the application of larval debridement therapy and some wounds with an ischaemic component). This can be controlled by reviewing the patient s analgesia for use prior to, and during, the treatment. If severe pain is experienced, it will be immediately alleviated if the larvae are removed and the wound is irrigated. As with any method of debridement, bleeding can result from damage to small capillaries and a regular daily inspection of the wound bed is recommended. 10. Interactions with other medical products Simultaneous treatment of the patient with systemic or topical cytostatic/cytotoxic substances would need to be discussed with the treatment prescriber. Topical disinfectants, local anaesthetics and some hydrogels (those that contain propylene glycol as a humectant and preservative) may have a negative effect on the growth and vitality of the larvae and, consequently, on the result of the treatment. Therefore, simultaneous treatment with the above substances should be avoided and any topical residues should be removed by irrigating the wound bed prior to the application of larval debridement therapy. Furthermore, factors such as radiation and reduced oxygen levels, e.g. caused by a too tight or occlusive secondary dressing, can lead to a decrease of the therapeutic outcome. The bagged larvae can be used in conjunction with a nonocclusive compression bandaging system. 6 Guidelines for the use of Larval Debridement Therapy

20 11. Choosing mode of application Investigations have demonstrated that free range and bagged larvae are equally efficacious in terms of debriding the wound (Blake et al, 2007). Two modes of treatment application are available and appropriate selection will depend on the following factors: Size of wound Depth of wound Location of wound Pre-existing or expected pain Patient acceptability (including mental capacity or concordance). 12. Application options Bagged larvae (BioBag) The larvae are sealed within a dressing which is a finely woven pouch containing a small piece, or pieces, of foam that protect the larvae during the early days of treatment. The BioBag dressings come in varying sizes and are applied according to the nature and size of the wound being treated. The larvae remain sealed within the dressing throughout the treatment. Dosage and duration of treatment: One or more BioBags should be applied to cover the entire area of devitalised tissue, taking care not to overlap the dressings. BioBags can be left in place for a maximum of four days, depending on the wound environment and the progress of the treatment. An application period of three days is typical. If the wound is not completely clean within four days, treatment can be repeated with a fresh BioBag. Treatment should be discontinued once the wound is suitably debrided, or if no progress can be observed after three or more applications. Figure 2. BioBag prior to application Figure 3. Applying the BioBag. Guidelines for the use of Larval Debridement Therapy 7

21 Free range larvae (Larvae300) The loose larvae are applied directly on to the wound and retained within a special dressing system. The exact nature of this is determined by the size and location of the area to be treated. Free range larvae are generally indicated for use on wounds where sufficient surface contact cannot be attained by bagged larvae and/or where the intention for usage is diagnostic to uncover the depth of tissue damage. Dosage and duration of treatment: According to published literature, five to eight free range larvae should be applied per cm 2 of necrotic/sloughy tissue. A larvae free range calculator can be of use in determining the approximate number of larvae required for treatment (See Prescribing and ordering page 11). Figure 4. Free range larvae (Larvae300) in transportation vial. Free range larvae can be left in place for a maximum of three days, depending on the wound environment and the progress of the treatment. An application period of three days is typical but if the wound is not completely clean within this time, treatment can be repeated with fresh free range larvae. Treatment should be discontinued once the wound is suitably debrided, or if no progress can be observed after three or more applications. Figure 5. Loose larvae. Figure 6. Larvae on the wound (Picture with permission of Julie Evans). 8 Guidelines for the use of Larval Debridement Therapy

22 13. Prescribing and ordering Using the BioBag size guide (see page 12), select the appropriate size of dressing, or combination of dressings, to cover the entire treatment area including margins. The Larvae free range calculator (see below) can be used to provide guidance on the number of larvae that should be used for each application. Ordering 1. Community orders will need to be raised on an FP10 prescription by a doctor or registered prescriber 2. Hospital orders should be written on the patient s prescription sheet according to local protocol for ordering 3. Ordering should be carried out by the community or hospital pharmacist (or stores) by phoning or faxing BioMonde (the single producer of larval debridement therapy) providing the following information: Size and quantity of BioBag dressings/number of pots and retention nets required Official order number Intended delivery date Full delivery address (all deliveries must be signed for) Invoice address. Orders can be accepted up to 2pm the day before the intended application date and delivery is available from Monday to Saturday. Storage Larvae should be kept in transit containers until application Store at a temperature of 6-25 C (products do not need to be refrigerated) Larvae should be applied by the expiry date for optimal results (up to 24 hours following delivery). Larvae free range calculator 1. Measure the dimensions of the wound in centimetres 2. Pick the nearest size from the measuremements on the left of the chart 3. Move sideways to the appropriate percentage of wound coverage 4. State the numbe of pots required from within the coloured cell. Maximum wound size Percentage of wound that is covered with slough/ necrotic tissue (cm) 20% 40% 60% 80% 100% Up to 2x x x x x x x x x x x x Note that the calculator only measures the surface of the wound. If the wound has significant depth, more larvae may be required. Guidelines for the use of Larval Debridement Therapy 9

23 BioBag sizes and codes BB x 10cm BB200 5 x 6cm BB x 6cm BB100 5 x 4cm BB x 4cm 10 Guidelines for the use of Larval Debridement Therapy

24 14. Step-by-step application instructions: BioBag Materials required for the application of BioBag: Single BioBag, or combination of BioBag sizes, suitable for the wound size A sterile wound cleansing pack/dressing pack. Zinc-based barrier cream or zinc bandage to protect intact periwound skin Sudocrem (Forest Laboratories UK Limited) or other suitable alternative An absorbent (non-occlusive) dressing pad and a lightweight retention bandage Sterile saline for irrigation of the wound or dressing residues and moistening of primary swab. Preparation of the wound site (figure 7): 1. Irrigate the wound to remove dressing residues and loose material 2. Protect intact periwound skin with a layer of zinc-based barrier cream (Sudocrem) or zinc bandage. Application of BioBag (figures 8 9): 1. Remove the BioBag from the transport vial 2. Place on to wound so that wherever possible the wound margin is covered and fold/double back away from the periwound skin 3. At the time of application, and subsequent dressing changes, place a moistened gauze swab over the BioBag dressing to ensure the larvae are dampened (especially if the wound is very dry) 4. Apply an absorbent outer dressing which should be selected to manage increased exudate and maintain a non-occlusive environment for the larvae 5. Finally, secure all dressings in place by taping outer edges of the absorbent dressing or apply a light bandage. barrier wound Figure 7. Prepare the wound site. BioBag dressing Figure 8. Place BioBag on wound. Place a moistened gauze swab over the BioBag dressing absorbent pad Figure 9. Ensure the larvae are moist. Guidelines for the use of Larval Debridement Therapy 11

25 15. Step-by-step application instructions: free range larvae Materials required for application of free range larvae: A sterile wound cleansing pack/dressing pack Sterile saline for irrigation of the wound and to remove the larvae from the transport vial Hydrocolloid to border the wound Sterile scissors for cutting retention net and hydrocolloid to size Retention net (flat net, boot net) Impermeable plastic adhesive tape, e.g. Leukoplast Sleek (BSN medical) (Note: other tapes may not retain the larvae). skin hydrocolloid dressing wound Figure 10. Use hydrocolloid sheet. Preparation of the wound site: Irrigate the wound to remove dressing residues and loose material. Application of free range larvae (flat net) (figures 10-16): 1. Ensuring the skin is dry and clean, place strips of hydrocolloid around the periwound area to protect the healthy skin from larval enzymes and increased exudate levels and also to serve as a border to fix the retention net. For a smaller wound a hole can be cut in the centre of the hydrocolloid matching the size of the wound. 2. Remove the larvae from the transport vial by adding approximately 5ml of sterile saline to the container and gently agitate to remove the larvae from the sides of the vial. If more than one pot of larvae is to be applied, tip the contents of the first container into the second and agitate as before. Repeat this process as many times as necessary adding additional saline as required. 3. Place the retention net provided (cut to size as required) on top of a sterile gauze swab and pre-moisten with saline to overcome surface tension effects and stop larvae moving off the net. Slowly pour the saline containing the larvae onto the net and invert the net onto the wound. Figure 11. Re-suspend the larvae. Figure 12. Wet the net. Figure 13. Pour out the larvae. 12 Guidelines for the use of Larval Debridement Therapy

26 4. Attach the net securely to the hydrocolloid border using the impermeable plastic adhesive tape, e.g. Sleek Tape. Ensure the tape does not come into contact with skin so as to avoid skin trauma in the way of skin stripping due to the adhesives in the tape. 5. Apply a saline-moistened swab over the outside of the net and cover with an absorbent pad. In the event of a dry wound environment, moisten the dressings to create an optimal environment for the larvae and the wound (the dressings should be moist to the touch but do not over saturate). Secure the dressings in place with a non-occlusive bandage or adhesive tape to ensure the adequate provision of oxygen to the wound surface. Occlusive dressings or film dressings should not be used, as these will cause larvae to suffocate. The dressing may be checked on a daily basis and the outer absorbent padding changed as required. Figure 14. Invert net over the wound. Sleek tape Figure 15. Tape the net in position. Figure 16. Bandage or secure as appropriate. Guidelines for the use of Larval Debridement Therapy 13

27 Application of free range larvae (using a boot net as a sleeve) 1. Cut boot net to size by cutting along the sealed edge to provide a net which is open at both ends 2. Fix hydrocolloid at either end of the area to be treated and tape one end of the sleeve to the hydrocolloid border prior to application of the larvae 3. Protect good skin from larval enzymes and increased exudate by applying a barrier cream, e.g. Sudocrem. 4. Transfer the larvae from the transport vial as per flat net application onto a pre-moistened sterile swab which can be used as a vehicle to transfer the larvae directly onto the wound bed by applying in a dabbing motion 5. Fix remaining end of the net in position and apply additional dressings as per flat net application. skin hydrocolloid dressing wound Figure 17. Hydrocolloid strips in position. hydrocolloid dressing sleek tape sleeve Figure 18. Checking for length of sleeve. Figure 19. Sleeve rolled back. 14 Guidelines for the use of Larval Debridement Therapy

28 Application of free range larvae (using a boot net) 1. Cut boot net to size, to be measured either to half way along the foot or to the ankle 2. Protect good skin from larval enzymes and increased exudate by applying a barrier cream, e.g. Sudocrem 3. Transfer the larvae from the transport vial as per flat net application onto a pre-moistened sterile swab which can be used as a vehicle to transfer the larvae directly onto the wound bed by applying in a dabbing motion 4. Secure boot net to the hydrocolloid border with adhesive tape (Sleek Tape) and apply ancillary absorbent dressings as per flat net application. Figure 20. Fix sleeve in position. Prepare the wound site hydrocolloid dressing wound hydrocolloid dressing barrier skin Hydrocolloid dressing in position for half boot dressing. Hydrocolloid dressing in position for whole boot dressing. Guidelines for the use of Larval Debridement Therapy 15

29 16. Looking after larval therapy (management plan) Bagged larvae (up to four days duration) 1. Check outer dressings daily and change where necessary (i.e. when saturated with exudate) 2. Reapply barrier where necessary to the periwound area 3. Ensure damp gauze is replaced on top of the bag at each secondary dressing change 4. Ensure that all outer/secondary dressings are not occlusive and are permeable to the air 5. Ensure that all secondary dressings are secured well to avoid slippage and to ensure surface contact of the bag is maintained 6. Do not immerse in water. Four-day cycle (BioBag) Free range larvae (up to three days duration) 1. Check outer/secondary dressings daily and change where necessary (i.e. when saturated with exudate) 2. Ensure damp gauze is replaced on top of the netting at each secondary dressing change 3. Ensure a good seal is maintained between the tape and the hydrocolloid border. 2. Check larvae are viable at secondary dressing changes movement of larvae and presence of dark red exudate are indications that larvae are alive 3. If the patient complains of pain and discomfort reassess and consider the appropriateness of continuing larval debridement therapy 4. Assess necessity for subsequent application 24 hours before the end of treatment. 17. Removal and disposal Removal Bagged larvae should be removed from the wound using a clean technique and disposed of according to local policy. When removing free range larvae, all outer dressings should be removed together with the hydrocolloid border. The larvae should then be gently wiped off or irrigated from the wound and disposed of according to local policy. Any larvae that have found their way into the depths of the wound will generally come to the surface if the wound is irrigated with a stream of sterile water or saline. If it is not possible to remove all the larvae, the wound may be covered with an occlusive dressing and the remainder will be broken down in the wound bed without any harm to the patient. Disposal Used larvae products and ancillary dressings should be regarded as potentially contaminated and disposed of in accordance with the local infection control policy. This normally involves placing them in clinical waste bags, which should be sealed and sent for destruction in the usual way. On the death of the patient In the event of a patient dying unexpectedly while receiving larval debridement therapy, the larvae should be removed from the wound prior to the transfer of the patient to the mortuary and disposed of as described above. Three-day cycle (Boot/Flat Net) General care instructions 1. If the application is to a pressure ulcer, ensure that there is no pressure on the larvae for the duration of the treatment (short periods of pressure for the purpose of mobilising are permissible) 18. Discharge guidance Patients who are being treated with larval debridement therapy can be discharged from secondary care to primary care if agreed in advance with the Practice/District Nursing teams who can ensure that there is a suitable level of home care has been established. An appropriate level of knowledge of receiving community healthcare professionals should also be established prior to discharge. 16 Guidelines for the use of Larval Debridement Therapy

30 References Blake F, Abromeit N, Bubenheim M, et al (2007) The biosurgical wound debridement: Experimental investigation of efficiency and practicability. Wound Repair Regen 15(5): Boulton A (2007) Maggots rid patients of MRSA, Press release. Available online at: (accessed 21 March 2013) Cazander G, van Veen KE, Bouwman LH, et al (2009) The influence of maggot excretions on PAO1 biofilm formation on different biomaterials. Clin Orthop Relat Res 467(2): Chan DC, Fong DH, Leung JY, et al (2007) Maggot debridement therapy in chronic wound care. Hong Kong Med J 13(5): Dowsett C (2002) The role of the nurse in wound bed preparation. Nurs Standard. 16(44): EWMA (2004) Position Document wound bed preparation in practice. MEP Ltd: London. Accessed online at: (accessed 12 March 2013) EWMA (2013). Debridement. An updated overview and clarification of the principle role of debridement. EWMA Document. Accessed online at: www. ewma.org Fletcher, J. (2005) Wound bed preparation and TIME principles. Nurs Standard. 20(12): Gottrup F, Jørgensen B (2011) Maggot debridement: an alternative method for debridement. Eplasty. 11:e33. Gray D, Acton C, Chadwick P, et al (2010) Consensus guidance for the use of debridement techniques in the UK. Wounds UK 7(1): Harris LG, Bexfield A, Nigam Y, et al (2007) Disruption of Staphylococcus epidermidis biofilms by medicinal maggot Lucilia sericata excretions/ secretions. Int J Artif Organs 32(9): Leaper D (2002) Surgical debridement. World Wide Wounds. Available online at: Debridement.html (accessed 12 March 2013). NICE (2001) Technology Appraisal Guidance 24: Guidance on the use of debriding agents and specialist wound care clinics for difficult to heal surgical wounds. NICE, London. Ousey K, Pankhurst S, Bale S, et al (2010) The Quality Agenda What does it mean for tissue viability? A Debate. Wounds UK 6(1): Schultz GS, Sibbald RG, Falanga V, et al (2003) Wound bed preparation: a systematic approach to wound management Wound Repair Regen 11(2): S1 S27 Vowden K, Vowden P (1999) Wound debridement Part 1: non-sharp techniques. J Wound Care 8(5): Weir D, Scarborough P, Niezgoda JA (2007) Wound debridement. In: Krasner DL, Rodeheaver GT, Sibbald RG (eds.) Chronic Wound Care: A Clinical Source Book for Healthcare professionals. 4th edn. HMP Communications, Malvern: Welsh Assembly Government (2005) Designed for Life-Creating World Class Health and Social Care for Wales. Welsh Assembly Government, Cardiff Wounds UK (2013) Effective debridement in a changing NHS. Wounds UK. Accessed online at: Guidelines for the use of Larval Debridement Therapy 17

31 Appendix 1: Frequently asked questions This section is intended to provide patients with information on larval therapy and give answers to some of the questions they might have What is larval therapy? Larval therapy, also known as maggot therapy or biosurgery involves the use of larvae of the greenbottle fly, which are introduced into a wound to remove necrotic sloughy and/or infected tissue. Larvae can also be used to maintain a clean wound after debridement if a particular wound is considered prone to resloughing. The technique, which has been used for centuries, has been reintroduced into modern medicine by doctors and wound care specialists who have found that larvae are able to cleanse wounds much more rapidly than conventional dressings. Whilst larvae should not be regarded as a cure for all types of wounds, by removing dead tissue and any associated bacteria, in most instances they will improve the condition of a wound and allow the process of healing to begin. How does larval therapy work? The processes by which larvae clean wounds are very complex, but in simple terms they physically feed on dead tissue and release special chemicals into the wound that breakdown dead tissue into a liquid form that the larvae can easily remove and digest. During this process the actively feeding larvae also take up bacteria, which are then destroyed within their gut. This process is so effective that larvae can often clean a wound within a few days. How big are the larvae? The larvae that are applied to your wound are very small only a few millimeters in length smaller than a grain of rice. During the treatment time they will increase in size as they clean the wound, to a maximum of 12mm. How are the larvae applied? There are two methods of application: 1) BioBag Dressing The larvae are sealed within a dressing which is a finely woven net pouch containing a small piece, or pieces of foam, which aid the growth of the larvae and manage exudate. The BioBag Dressings come in varying sizes and are applied according to the nature and size of the wound being treated. The larvae remain sealed within the dressing throughout the treatment. 2) Free Range Larvae The larvae are applied directly onto the wound and retained within a special dressing system. The exact nature of this is determined by the size and location of the area to be treated. How long does the treatment last? This can vary with each treatment of larvae and the method of application being used. BioBag Dressings can be left in place for up to four days; it is possible for the dressing to be removed on a daily basis to allow inspection of the wound site. Free range larvae are generally left in place for up to three days before being removed from the wound site. With both application methods, it is impossible to predict how long a course of treatment will take. Sometimes a wound is completely cleansed by a single application of larvae but other wounds may require two or more treatments to achieve the desired effect. Will I notice anything different during larval therapy? During larval therapy you may notice some changes in the wound: The wound may become a little wetter than usual or show the presence of a dark red or pink discharge. This is due to the action of the larvae breaking down the dead tissue. Sometimes a wound that contains a lot of dead tissue will develop a characteristic smell during treatment. This is nothing to worry about, it is just due to the activity of the larvae and should disappear when the dressing is changed. Most people are unaware of the larvae s presence, although a small number of patients claim that they can feel the larvae moving but only describe this as a tickling sensation. Some patients, particularly those with poor circulation, report that their wounds become more painful during larval therapy but this can generally be controlled with medication. Some patients have found that the pain associated with infected wounds is reduced following larval therapy. 18 Guidelines for the use of Larval Debridement Therapy

32 Will larvae burrow into healthy tissue? The larvae used in wound management will not attack or burrow into healthy tissue, they only remove dead tissue. Will the larvae multiply in my wound? Only adult flies can lay eggs, so the larvae cannot reproduce or multiply within the wound. Where do the larvae come from? Larvae are produced in a special unit by highly trained staff at BioMonde, a company with many years experience in wound management. Are there any activities that should be avoided during treatment? Although it is possible for the patient to carry out most normal activities whilst undergoing larval therapy, they should ideally not bathe or immerse the wound in water. It is also not a good idea to sit with the wound too close to a source of heat e.g. fire or radiator, as the larvae may dry out. Similarly, sitting or walking on a wound treated with larvae should also be avoided as much as possible. Why use larval therapy instead of a conventional dressing? Clinical experience with larvae has shown that they can clean wounds in a fraction of the time taken by more conventional dressings, which could potentially speed up healing times. They are also useful in the management of infected wounds containing bacteria that are difficult to kill with more conventional treatments. Larvae have also been shown to be successful at eliminating MRSA from wounds. What is the ethical position relating to the use of larvae? The use of larvae in wound management has a sound basis in literature. It appears to be free of any serious or significant side effects and can have major advantages over conventional treatments for certain types of wounds. Provided that a specific patient has no objection to the use of larvae there appear to be no ethical barriers to their use. Further Information: Healthcare Professional Competences: See Agored Cymru Support from BioMonde : Healthcare Professionals: After 5pm Monday to Friday, and all day Saturday and Sunday. Clinical Helpline: Guidelines for the use of Larval Debridement Therapy 19

33 20 Guidelines for the use of Larval Debridement Therapy

34 Guidelines for the use of Larval Debridement Therapy 21

35 All Wales Tissue Viability Nurse Forum, 2013

36 Looking after your Larval Therapy BioBag daily care Do not immerse in water. Do not occlude Avoid sustained, direct pressure as this may occlude the larvae. Short periods for the purposes of mobilisation are permissible Daily change of the secondary dressings is recommended and when strikethrough is present Re-apply barrier where necessary to the peri-wound area (fig.1) Check larvae are viable at secondary dressing changes movement of larvae and presence of dark red exudate indicate the larvae are alive (fig.2) Ensure damp gauze and an absorbent pad are replaced on top of the BioBag at each secondary dressing change (fig.3) Ensure that all outer/ dressings are not occlusive and are permeable to the air (fig.4) After 72 hours, reassess wound to decide on further treatment. If a further NEW larval treatment is required, schedule a new order If debridement is near completion and no further NEW larval treament is required, plan follow on care/dressings as per specialist instructions or local formulary On removal, double bag and treat as clinical waste in line with your local Grade A Clinical Waste Disposal Protocol. 4 Day Treatment Cycle 0hrs 24hrs 48hrs 72hrs 96hrs Application of larvae Assess and reorder (if required) Daily Care Daily Care Daily Care Daily Care Repeat as required Remove and dispose Fig.1 Re-apply barrier cream Fig.2 Check larvae are viable, reposition BioBag if necessary Fig.3 Place a moistened gauze swab over the BioBag Fig.4 Secure the moistened swab and absorbent pad Skin Wound BioBag Moistened Gauze Barrier How to store and order BioBag sizes and codes Ordering Larvae Storage Code Description BioBag BB50 2.5x4cm BB100 5x4cm BB200 5x6cm BB300 12x6cm BB400 10x10cm Orders received by us before 2pm will qualify for inclusive next day delivery, or a future planned date of your choosing. Please allow time for your own internal procurement/pharmacy to process the order. Telephone: orders@biomonde.com Fax : Office Hours Monday to Friday 8:30am 5:00pm For assistance outside working hours please call our Clinical Helpline: Keep in transit containers Store at a temperature of 6 C to 25 C (products do not need to be refrigerated) Must be applied by expiry date; usually the day after delivery. For optimal results apply on day of delivery. BM110_05_0713/IP Making healing possible

37 Making healing possible Patients & Carers Guide Answers to your common questions

38

39 If you are reading this, it is likely that you are considering larval therapy as part of a course of wound treatment. This booklet is intended to provide you with information on the technique and give answers to some of the questions you might have about the therapy. What is larval therapy? Larval Therapy, also known as Maggot Therapy or Biosurgery involves the use of larvae of the greenbottle fly, which are introduced into a wound to remove necrotic, sloughy and/or infected tissue. Larvae can also be used to maintain a clean wound after debridement if a particular wound is considered prone to resloughing. The technique, which has been used for centuries, has been reintroduced into modern medicine by doctors and wound care specialists who have found that larvae are able to cleanse wounds much more rapidly than conventional dressings. Whilst larvae should not be regarded as a cure for all types of wounds, by removing dead tissue and any associated bacteria, in most instances they will improve the condition of a wound and allow the process of healing to begin. How does larval therapy work? The processes by which larvae clean wounds are very complex, but in simple terms they physically feed on dead tissue and release special chemicals into the wound that

40 breakdown dead tissue into a liquid form that the larvae can easily remove and digest. During this process the actively feeding larvae also take up bacteria, which are then destroyed within their gut. This process is so effective that larvae can often clean a wound within a few days. How big are the larvae? The larvae that are applied to your wound are very small, only a few millimetres in length, smaller than a grain of rice. During the treatment time they will increase in size as they clean the wound, to a maximum of 12mm. How are the larvae applied? There are two methods of application: 1) BioBag Dressing The larvae are sealed within a dressing which is a finely woven net pouch containing a small piece, or pieces of foam, which aid the growth of the larvae and manage exudate. The BioBag Dressings come in varying sizes and are applied according to the nature and size of the wound being treated. The larvae remain sealed within the dressing throughout the treatment. 2) Free Range Larvae The larvae are applied directly onto the wound and retained within a special dressing system. The exact nature of this is determined by the size and location of the area to be treated.

41 How long does the treatment last? This can vary with each treatment of larvae and the method of application being used. BioBag Dressings can be left in place for up to four days; it is possible for the dressing to be removed on a daily basis to allow inspection of the wound site. Free Range larvae are generally left in place for up to three days before being removed from the wound site. With both application methods, it is impossible to predict how long a course of treatment will take. Sometimes a wound is completely cleansed by a single application of larvae but other wounds may require two or more treatments to achieve the desired effect. Will I notice anything different during larval therapy? During larval therapy you may notice some changes in the wound: The wound may become a little wetter than usual or show the presence of a dark red or pink discharge. This is due to the action of the larvae breaking down the dead tissue. Sometimes a wound that contains a lot of dead tissue will develop a characteristic smell during treatment. This is nothing to worry about, it is just due to the activity of the larvae and should disappear when the dressing is changed. Most people are unaware of the larvae s presence, although a small number of patients claim that they can feel the larvae moving but only describe this as a tickling sensation. Some patients, particularly those with poor circulation report that their wounds become more painful during larval therapy but this can generally be controlled with medication. Some patients have found that the pain associated with infected wounds is reduced following larval therapy.

42 Will larvae burrow into healthy tissue? The larvae used in wound management will not attack or burrow into healthy tissue, they only remove dead tissue. Will the larvae multiply in my wound? Only adult flies can lay eggs, so the larvae cannot reproduce or multiply within the wound. Where do the larvae come from? Larvae are produced in a special unit by highly trained staff at Biomonde, a company with many years experience in wound management. Are there any activities that should be avoided during treatment? Although it is possible for the patient to carry out most normal activities whilst undergoing larval therapy, they should ideally not bathe or immerse the wound in water. It is also not a good idea to sit with the wound too close to a source of heat e.g. fire or radiator, as the larvae may dry out. Similarly, sitting or walking on a wound treated with larvae should also be avoided as much as possible.

43 Why use larval therapy instead of a conventional dressing? Clinical experience with larvae has shown that they can clean wounds in a fraction of the time taken by more conventional dressings, which could potentially speed up healing times. They are also useful in the management of infected wounds containing bacteria that are difficult to kill with more conventional treatments. Larvae have also been shown to be successful at eliminating MRSA from wounds. What is the ethical position relating to the use of larvae? The use of larvae in wound management has a sound basis in literature. It appears to be free of any serious or significant side effects and can have major advantages over conventional treatments for certain types of wounds. Provided that a specific patient has no objection to the use of larvae there appear to be no ethical barriers to their use. For more information, Healthcare Professionals: Patients: Please contact your Healthcare Professional

44 Ordering Fax For assistance outside normal working hours, please call our Clinical Helpline After 5pm Monday to Friday, and all day Saturday and Sunday For further information, please get in touch using the contact information below. Our staff are available to provide both technical and clinical advice on all aspects of using Larvae. For product information and application guides in another language, please see our website. BioMonde Units 2 4 Dunraven Business Park, Coychurch Road, Bridgend, CF31 3BG United Kingdom Telephone: +44 (0) Facsimile: +44 (0) enquiries@biomonde.com BM53_05_0413/IP

45 Product Sizes and Codes BioBag Sizes & Codes BB x 10 cm BB x 4 cm BB100 5 x 4 cm BB200 5 x 6 cm BB x 6 cm Maximum Percentage of wound covered with slough/necrotic tissue wound size (cm) 20% 40% 60% 80% 100% up to 2 x x x x x x x x x x x x Free Range Calculator 1. Measure the dimensions of the wound in centimetres 2. Pick the nearest size from the measurements on the left of the chart 3. Move sideways to the appropriate percentage of wound coverage 4. State the number of pots required from within the coloured cell Note that the calculator only measures the surface of the wound. If the wound has significant depth, more larvae may be required. BM48_06_0413/IP

46 Free Range Larvae sizes & codes Code Description Community STKIT1 Larvae and 30x30cm retention net kit pack with 1 vial STKIT2 Larvae and 30x30cm retention net kit pack with 2 vials STKIT3 Larvae and 30x30cm retention net kit pack with 3 vials BTKIT1 Larvae and Boot retention net kit pack with 1 vial BTKIT2 Larvae and Boot retention net kit pack with 2 vials BTKIT3 Larvae and Boot retention net kit pack with 3 vials Hospital STVIAL1 Larvae and 30x30cm retention net with 1 vial STVIAL2 Larvae and 30x30cm retention net with 2 vials STVIAL3 Larvae and 30x30cm retention net with 3 vials BTVIAL1 Larvae and Boot retention net with 1 vial BTVIAL2 Larvae and Boot retention net with 2 vials BTVIAL3 Larvae and Boot retention net with 3 vials How to Order Using the BioBag size guide, select the appropriate sized dressing or combination of dressings to cover the entire treatment area including margins. A retention net is required to apply free range Larvae to a wound. These nets are also available from us. Remember that the net dressing must always overlap the wound and in the case of circumferential wounds, the net sleeves must extend beyond the length of the wound. The Larvae Calculator can be used to provide guidance on the number of larvae that should be applied in each application. The calculator is freely available either as a hard copy from BioMonde or by downloading it from our website. Ordering information Community i. Community orders will need to be raised on an FP10 prescription by a doctor or registered prescriber ii. Intended delivery date required iii. Community pack size required iv. Full delivery address (please note that all deliveries must be signed for) v. Invoice address required Ordering information Hospital i. Size and quantity of BioBag Dressings / number of pots and retention nets required ii. Official order number iii. Intended delivery date required iv. Full delivery address (please note that all deliveries must be signed for) v. Invoice address required Orders will be accepted up to 2pm the day before the intended application date. To cancel an order, please contact BioMonde before 2pm on the day before delivery, all cancellations received after this time must be paid for in full as the order will have been despatched for delivery. Orders can be placed by telephone on or by fax on

47 EVIDENCE-BASED PRACTICE Larval debridement therapy: an economic, scientific and clinical evaluation Wounds UK Supported by BioMonde

48 EVIDENCE-BASED PRACTICE PUBLISHED BY: Wounds UK Enterprise House 1 2 Hatfields London SE1 9PG, UK Tel: + 44 (0) Fax: +44 (0) Wounds UK 2013 This document has been developed by Wounds UK and supported by an unrestricted educational grant from BioMonde. For further information about the products used, please visit: The views expressed are those of the authors and do not necessarily reflect those of BioMonde. How to cite this document: Larval debridement therapy. An economic, scientific and clinical evaluation. London: Wounds UK 2013; 9(4) Suppl. Available to download from: 1 Wounds UK LDT: An economic, scientific and clinical evaluation Nov (4) Suppl

49 EVIDENCE-BASED PRACTICE Larval debridement therapy: its role in chronic wound healing Larval therapy, also known as maggot therapy or biosurgery, has a long history of use in the treatment of chronic and infected wounds. Larvae were first used for debridement in the American Civil War and First and Second World Wars and were used successfully to treat several cases of osteomyelitis (Buchman and Blair, 1932). With the advent of antibiotics in the 1940s, however, the practice of larval debridement therapy (LDT) declined. More recently, interest in LDT has resurged due in part to the rise in chronic wounds and the emergence of antibiotic resistant strains of bacteria, such as meticillin-resistant Staphylococcus aureus (MRSA) (Davies, 2013). This has necessitated finding other effective methods to facilitate cleansing and removing necrotic material, and combat infection without damaging the healthy tissue beneath. Debridement should be considered as an essential part of the process of caring for a patient with a wound (Wounds UK, 2013). However, although there is currently no robust evidence to support any particular method of debridement, it is generally accepted that necrotic/infected tissue must be removed as quickly and efficiently as possible (Wounds UK, 2013). In this document, Bennett et al (pp2 11) describe a first attempt to evaluate the cost-effectiveness of LDT compared to all relevant comparator therapies in UK clinical practice. Although the data limitations mean there is a degree of uncertainty in the results, the model provides useful information on the comparative costs and benefits of debridement therapies, with LDT remaining cost-effective under all scenarios tested in a range of sensitivity analyses. This important study identifies gaps in available evidence relating to debridement and highlights the need for further research, particularly in the areas of quality of life and resource use to support clinical decision-making. Effective debridement can help progress a wound to healing and is associated with reduced exudate, a reduction in odour and the appearance of granulation tissue in the wound bed (Vowden and Vowden, 2011). Larvae of the greenbottle fly (Lucilia sericata) physically feed on dead tissue, cellular debris and exudate present in sloughy wounds. This process involves the physical actions of the larvae and presence of proteolytic enzymatic digestion in the wound. The second paper in this document by Dr Yamni Nigam (pp12 16) reviews the scientific studies that explain the actions of LDT in chronic and infected wounds. These confirm the role of larvae in wound debridement, while shedding new light on their antibacterial activity: larval secretions may have a significant inhibitory effect on bacteria and be capable of disrupting biofilms, which are even harder to eradicate. Larval secretions may also be important in reducing chronic inflammation, helping to steer the wound towards healing. Science is starting to tell us a great deal about the mechanisms that underlie the actions of larvae; clearly, this is just the beginning and much more work is required. In the third paper, Perricone et al (pp17 19), describe setting up the LDT service at the Blackpool Teaching Hospitals. This was initially established within the hospital and led by the vascular team with involvement of the tissue viability nurse advisor. Subsequently, the service has expanded to include community care, providing patients with good access to LDT. Although the initial intention was to target hospital patients who were unfit for surgical intervention, larval therapy is no longer used as a last resort; rather it is being used proactively to clean and close wounds quickly. However, these clinicians recognise the need to quantify the clinical and cost benefits of LDT and the vascular team is currently undertaking a case-series evaluation using medical photography, data collection and follow-up. They hope this will lead to more appropriate referrals and ultimately help to improve patient outcomes. REFERENCES Buchman J, Blair JE. Maggots and their use in the treatment of chronic osteomyelitis. Surg Gynecol Obstet 1932;55: Davies SC (2013) Annual Report of the Chief Medical Officer. Volume Two, Infections and the Rise of Antimicrobial Resistance. Department of Health, London. Available at: bit.ly/zjyqlz (accessed ) Vowden P, Vowden K (2011) Debridement Made Easy. Wounds UK 7(4). Available from: Wounds UK (2013) Effective debridement in a changing NHS. A UK consensus. Wounds UK. Available from: www. wounds-uk.com KEITH HARDING Dean of Clinical Innovation, Head of Wound Healing Research Unit, Cardiff University Wounds UK LDT: An economic, scientific and clinical evaluation Nov (4) Suppl 2

50 Cost-effectiveness of interventions for chronic wound debridement: an evaluation in search of data KEY WORDS Wound debridement Economic evaluation Cost-effectiveness Cost utility Standard practice in the management of chronic hard-to-heal wounds includes debridement; however, to date, no comprehensive economic evaluations of all debridement interventions available in the UK have been reported. Aims: This analysis set out to evaluate the cost-effectiveness of larval debridement therapy (LDT) compared with all relevant comparator therapies in UK clinical practice. Methods: A decision-tree model was developed to represent the typical treatment of a single patient in clinical practice, comprising a series of monthly treatment cycles over 12 months. Results: Initiating treatment with LDT is estimated to be a less costly and more effective debridement strategy than initiating treatment with any of the comparator debridement methods evaluated in the base case. Data limitations and necessary modelling assumptions lead to considerable uncertainty in the modelling results; however, LDT remained cost-effective under all scenarios tested in a range of sensitivity analyses. Conclusions: The authors suggest that to understand better the comparative costs and benefits of debridement therapies and to support evidence-based decision-making, further research is needed to improve evidence in this area, particularly relating to quality of life and the resource use associated with therapies to which cost-effectiveness results were sensitive. HAYLEY BENNETT, Research Officer, Swansea Centre for Health Economics, Swansea University BERNADETTE SEWELL, Research Officer, Swansea Centre for Health Economics, Swansea University PIPPA ANDERSON, Director, Swansea Centre for Health Economics, Swansea University MAHENDRA KUMAR RAI, Senior Consultant, Health Outcomes Research, Knowledge Services Capita India Pvt. Ltd. RICHA GOYAL Consultant, Health Outcomes Research, Knowledge Services Capita India Pvt. Ltd. CERI PHILLIPS, Professor, Swansea Centre for Health Economics, Swansea University The efficient and effective allocation of healthcare resources is vital in the UK and elsewhere in Europe, as the pressure of delivering high-quality healthcare within a finite budget increases. Healthcare decision-making must be grounded in evidence and incorporate information about both the costs and benefits (health outcomes) of healthcare interventions. Economic evaluations provide this synthesis of economic and clinical Box 1: Different types of economic evaluation Cost-minimisation analysis (CMA): outcomes of the two (or more) comparators are assumed equal, thereby resulting in an assessment based solely on comparative cost. Making the assumption of equal outcomes rarely holds in practice. Cost-effectiveness analysis (CEA): outcomes are one dimensional and measured in naturally occurring units, such as changes in blood pressure or mortality. The incremental cost-effectiveness ratio (ICER) is calculated to determine the additional cost incurred to achieve an additional unit of outcome. If one intervention is both more expensive and more effective than its comparators, lower ICER values represent better value for money and a value judgement will be required to assess whether the cost per extra unit of outcome is worthwhile. information, comparing one intervention with a competing alternative in terms of both their costs and consequences. Such analyses may be undertaken prospectively, for example, alongside a randomised controlled trial (RCT), or through decision analytic modelling approaches. Box 1 below summarises the different types of economic evaluation that can be undertaken in healthcare. Cost-utility analysis (CUA): an extension of costeffectiveness analysis in which multi-dimensional health outcomes are reduced to a single index using health utilities and are expressed as quality adjusted life years (QALYs). The use of a standard measure of health benefit enables broader comparisons of costeffectiveness to be made across different diseases and populations. Cost-benefit analysis (CBA): costs and outcomes are valued in a common unit usually money. The financial value of the benefits is compared to the costs, allowing the selection of the intervention with the overall highest financial benefit. 3 Wounds UK LDT: An economic, scientific and clinical evaluation Nov (4) Suppl

51 EVIDENCE-BASED PRACTICE In the UK, CUA is the preferred approach to economic evaluation used by national bodies such as the National Institute for Health and Care Excellence (NICE), the Scottish Medicines Consortium (SMC) and the All Wales Medicines Strategy Group (AWMSG) when making decisions about what interventions should be used in the UK. Chronic wounds Chronic wounds affect hundreds of thousands of people, particularly older people. These wounds are painful and debilitating, resulting in reductions in quality of life. In 2007, Posnett and Franks estimated that chronic wounds affected 200,000 individuals annually in the UK, at a cost to the NHS of billion per year (2005/6 prices). Wound debridement Standard practice in the management of chronic hard-to-heal wounds includes debridement to remove dead tissue and activate healing by removing slough, exudate and bacteria. A variety of approaches may be used to accomplish this, including larval debridement therapy (LDT), autolytic dressings (hydrogel, honey), mechanical (ultrasound), and surgical treatments (including sharp debridement and hydrosurgical). An economic evaluation comparing LDT to hydrogel was conducted alongside the VenUS II (Dumville, 2009) RCT of LDT in the management and healing of leg ulcers; however, to date, no comprehensive economic evaluations of all debridement interventions available in the UK have been reported. The aim of this analysis was to evaluate costeffectiveness of LDT in wound debridement compared to all relevant comparator debridement therapies available in UK clinical practice, in the form of a CUA. METHODS The evaluation reported here was conducted from the perspective of the UK National Health Service (NHS) and Personal and Social Services (PSS) and was informed by relevant peer-reviewed publications, clinical experts in wound care and current clinical practice in the UK. After initial discussions with clinical experts, a structured literature review (to be reported elsewhere), was undertaken to support the development of a model evaluating the cost-utility of LDT against six comparator debridement therapies: mechanical, hydrogel, honey, surgical, sharp, and hydrosurgical. Identified literature describing economic evaluations, RCTs, observational studies and reviews published between January 2006 and December 2011 were reviewed to provide clinical and economic data for modelling. The review highlighted a dearth of good quality studies published in recent years that evaluated clinical- and/or cost-effectiveness of therapies for the debridement of wounds and promotion of healing, not only for LDT, but for all methods of debridement. Given this problem, where the literature review did not provide sufficient data to define and populate the model fully, health professionals in the field of wound care were consulted to inform plausible assumptions. Model description A decision-tree model was developed in Microsoft Excel to replicate the typical treatment of a single patient and is, of necessity, a simplification of the complex treatment of wounds and patient care in real life. Not all forms of debridement are suitable for all wounds and patients; however, this complexity is not represented in the model and comparisons are made only for those wounds for which the considered debridement therapies are appropriate. There is considerable variation in wound care and the treatment pathways seen for debridement in a clinical setting may differ depending on whether care is led by a vascular team or tissue viability nurse. Despite this variation of practice this model aims to represent an average case. Expert clinical opinion informed a number of assumptions incorporated in the model structure (Box 2), which comprised a series of monthly cycles over a one-year horizon. A basic schematic of the model is presented in Figure 1. A patient entering the model receives the debridement therapy of interest during Month 1 (LDT or one of its comparators). If debridement is not achieved during this period, the patient may receive a different therapy in the next cycle or undergo a clinical intervention, terminating the use of all debridement therapies. Up to six cycles of debridement therapy are modelled in total, after which any undebrided wound leads to clinical intervention. Within the six-month treatment period, patients are assumed to move from one therapy to another with equal probability, with the exception of surgicaltype therapies: surgical, sharp and hydrosurgical KEY POINTS Healthcare spending is under pressure in publically-funded health services. Chronic hard-to-heal wounds are a considerable burden on health services and have a high human impact. Wound debridement is standard practice to activate healing, but few clinical and economic evaluations are found in the literature. Economic evaluation of available wound debridement interventions is important to support healthcare decisionmaking, but lack of data makes this type of evaluation challenging. Estimates from economic modelling reported here suggest that initiating debridement with LDT is a cost-effective strategy. Wounds UK LDT: An economic, scientific and clinical evaluation Nov (4) Suppl 4

52 EVIDENCE-BASED PRACTICE Box 2: Key modelling assumptions The same debridement therapy is not used in consecutive months Surgical, sharp and hydrosurgical debridement therapies are not used in consecutive months The probability of clinical intervention increases over time for wounds not debrided at the end of a cycle of treatment Amputation (lower limb) is the clinical intervention modelled as the terminating event for the treatment of undebrided wounds The probability of clinical intervention is higher for autolytic therapies, based on the rates of amputation reported by Ribu et al (2008 ) A fixed cost and effect was applied to the probability of wound infection with each treatment Biosurgical [+] Mechanical [+] Debridement Hydrogel [+] Biosurgical Mechanical [+] No debridement Honey Surgical Sharp [+] [+] [+] Wound Hydrogel [+] Hydrosurgical [+] Honey [+] Clinical intervention Surgical Debridement Biosurgical [+] No debridement Mechanical [+] Sharp [+] Hydrogel [+] Hydrosurgical [+] Honey [+] Clinical intervention 1 Month Key: Decision node Chance node Terminal node [+] Branches repeated Figure 1: Schematic representation of the costeffectiveness model. debridement. Based on expert advice, more than one attempt may be made to achieve debridement with surgical-type therapies within a one-month cycle, although the number of procedures is restricted by the risks associated with general anaesthesia. As with other therapies, if debridement is not achieved with this therapy within one month, a different therapy may be used in the following month; however, surgical-type therapies will not be used successively. Based on an informed, simplifying assumption, all terminating clinical interventions were modelled as amputation relating to a lower limb or foot wound. In practice, patients might alternatively receive angioplasty, or other major interventions that address the underlying clinical problem responsible for the non-healing wound. This assumption may be considered conservative since other options may deliver greater post-intervention quality of life, while the modest difference in costs between interventions is unlikely to have a significant impact on the analysis. Clinical effectiveness Parameter values for the following variables were derived from the published literature where possible and based on informed assumptions where required: probability of debridement; probability of infection; probability of adverse events during treatment; and probability of clinical intervention (Table 1). 5 Wounds UK LDT: An economic, scientific and clinical evaluation Nov (4) Suppl

53 EVIDENCE-BASED PRACTICE Preference was given to information related to bagged larvae where data for both loose and bagged larvae were reported in the literature, as it is the most commonly used form of LDT currently commercially available. Rates of clinical intervention In the base case scenario, clinical intervention (amputation) rates were assumed to be low during the first six months of treatment. After the first month of debridement therapy, 0.5% of modelled patients who had undergone unsuccessful LDT, mechanical, surgical, sharp, or hydrosurgical debridement, received clinical intervention and ceased debridement therapy. Over the following months, the modelled proportion of patients with undebrided wounds receiving clinical intervention rose: 0.5%, 1%, 2% and 2.5%. The equivalent rates for autolytic therapies were 1%, 1%, 2%, 4% and 5%. At the end of Month 6, any wounds still not debrided resulted in a clinical intervention. Healthcare resource use and cost data Table 2 details the cost inputs implemented in the base case. Where available healthcare resource use and costs were derived from published sources, PSSRU Unit Costs (2011) and National Reference Costs (2011). Where necessary published costs were inflated to 2010/2011 costs using appropriate OECD PPP indices (OECD, 2010/11). Where published resource use and related cost data were not available, estimates were elicited from clinical experts based on their experiences of current practice. The cost of LDT, published by Dumville et al (2009), was updated and calculated from the weighted average cost per treatment from the manufacturer s (Biomonde Ltd) sales data (Data on file), to determine a cost per application of LDT ( 234). This cost is higher than the costs of LDT used by Dumville et al (2009) and, thus, any bias introduced by its implementation will be in favour of the comparator therapies. Quality Adjusted Life Years To calculate quality adjusted life years (QALYs), utility values * were required to weight the life years associated with the various treated and untreated health states within the model. These were derived from published literature where possible and assumptions made based on other treatment outcomes where necessary. Parameter values derived were baseline utility, utility associated with therapies, decrement of infection (per event), utility after clinical intervention (amputation), and decrement of utility related to other adverse events (Table 2). *a measure that represents preference based valuation of quality of life in a particular health state. Table 1: Clinical effectiveness data input parameter values in the base case analysis Debridement Therapy Biosurgical LDT Mechanical Ultrasound Parameter Value Data source Value Data source Number of treatments conducted Hydrogel Autolytic Surgical Sharp Hydrosurgical Honey Value Data source Value Data source Value Data source Value Data source Value Data source N/A N/A N/A N/A N/A N/A N/A N/A 1.91 Granick et al (2006) 2 Assumption based on Granick et al (2006) from Granick et al (2006) and 1.4 from Mosti et al (2005) Probability of debridement 76.70% Bagged larvae; Dumville et al (2009) 60.00% Assumption based on other data and expert opinion 63.20% Dumville et al (2009) 60.00% Assumption based on other data and expert opinion 95.00% Expert opinion 95.00% Expert opinion 95.00% Granick et al (2006) Probability of infection per month of treatment 17.50% Bagged larvae; Dumville et al (2009) 25.00% Assumption based on other data and expert opinion 26.00% Dumville et al (2009) 44.40% Gethin & Cowman (2009) 21.00% Assumption based on other data 25.00% Assumption based on other data 25.00% Assumption based on other data Probability of treatment related adverse events during treatment 9.60% Bagged larvae; Dumville et al (2009) 5.35% Assumption based on other data and expert opinion 7.70% Dumville et al (2009) 7.70% Assumption based on other data and expert opinion 5.35% Caputo et al (2008) 5.35% Caputo et al (2008) 5.35% Caputo et al (2008) Wounds UK LDT: An economic, scientific and clinical evaluation Nov (4) Suppl 6

54 EVIDENCE-BASED PRACTICE RESULTS As an indicator of value for money, incremental cost effectiveness ratios (ICERs) were calculated based on the difference in costs incurred and benefits provided by LDT compared to the named comparator. In the UK, the commonly accepted norm for a new intervention to be adopted is 20,000 per QALY gained. This is much the same as in other European jurisdictions and we have used this as our benchmark for acceptable cost-effectiveness. The results for the base case CUA of LDT versus each of the comparator debridement methods are shown in Table 3. Figure 2 shows that all plots of incremental costs and QALYs estimated for LDT, compared with all alternatives, fall in the lower right quadrant of the cost-effectiveness plane. Thus, LDT appears to be the dominant therapy ie it is expected to be more effective and less costly than all alternatives considered. Sensitivity analysis The limited availability of data and variation in clinical wound care and debridement practice lead to a high degree of uncertainty surrounding the data inputs and assumptions made during the development of the model. The potential consequences of this uncertainty were explored through sensitivity analysis, as follows. Hydrosurgical therapy Although surgical-type debridement is typically achieved with approximately two attempts, hydrosurgical therapy was reported in two published studies to require an average of only 1.18 or 1.4 attempts to achieve debridement (Granick, 2006; Caputo, 2008). A fairly conservative estimate of the number of hydrosurgical procedures conducted (1.2) was taken in the base case. Varying the number of hydrosurgical procedures (n=1.18, 1.4, 1.9) had little impact on the incremental results and none on the overall costeffectiveness conclusions. Clinical (terminating) interventions The rates of clinical intervention (amputation) over time could not be identified in the literature and are subject to uncertainty as a result. Based on the higher rates of amputation reported for autolytic therapies (Ribu et al, 2008), the base case assumes higher rates of clinical intervention over time for hydrogel and honey compared to other initial therapies. To test the consequences of uncertainty around these assumptions, two scenario analyses were conducted. Firstly, a more gradual increase of clinical intervention was applied over time, escalating to the assumption of clinical intervention for all undebrided wounds at the end of six months; and secondly, the same rates were assumed across all therapies (including autolytic). Table 2: Cost and health related utility data input parameter values in the base case analysis Costs Health utilities Parameter Value Data source(s) Parameter Value Data source Cost of therapy (per month or procedure) LDT Mechanical Ultrasound Autolytic Hydrogel Autolytic Honey Surgical Sharp Hydrosurgical ,320 1,370 2,620 Soares et al (2009), Hall et al (2010) Watson et al (2011) Dumville et al (2009) Expert opinion NHS Reference costs 2010/11 NHS Reference costs 2010/11 Granick et al (2006) (converted to GBP) Health utility associated with therapy LDT Mechanical - Ultrasound Autolytic Hydrogel Autolytic Honey Surgical Sharp Hydrosurgical Soares et al (2009), Dumville et al (2009) Watson et al (2011) Dumville et al (2009) Assumption (expert opinion) Assumption (expert opinion/other therapy values) Assumption (expert opinion/other therapy values) Assumption (expert opinion/other therapy values) Infection 621 NHS Reference costs 2010/11* Baseline utility value of uninfected wound 0.6 Iglesias et al (2004) Clinical intervention 6,508 NHS reference costs 2010/11: weighted cost of amputation with/ out major cc (40%) and foot procedures (60%) according to Ribu et al (2008) Decrement of infection (per event) Nelson et al (2006) Adverse events 36 GP visit PSSRU Unit Costs 2011** After clinical intervention 0.54 Nelson et al (2006); relating to amputation *Department of Health. NHS Reference costs 2010/11. Accessed October 2012 **Curtis L. Unit Costs of Health and Social Care. Kent: Personal Social Services Research Unit, Accessed October Wounds UK LDT: An economic, scientific and clinical evaluation Nov (4) Suppl

55 EVIDENCE-BASED PRACTICE Table 3: Base case incremental results of LDT compared to alternative debridement therapies Debridement comparison made with LDT Incremental cost Incremental QALYs ICER vs. surgical - 3, Dominant vs. sharp - 1, Dominant vs. hydrosurgical - 2, Dominant vs. mechanical (ultrasound) Dominant ,000-1,500-2,000-2,500-3,000 Incremental cost / patient - 3,500-2,500-2,500-3,000-3,000-2,000-3,000-4,000-3,000-3,000-3,500-3,500-2,500-3,500-3,500-3,500-4,000-4,000-3,000-4,000-4,000 vs. hydrogel Dominant vs. honey Dominant ,000-1,000-1, ,500-1,500-1,000-1,000-1, ,500-2,000-2,000-1,500-2,000-1,000 Incremental QALY / patient ,000-2,000-2,500-2,500-2,500-1, Comparator Surgical Sharp Hydrosurgical Mechanical Hydrogel Honey 20,000 threshold Figure 2: Graphical representation of base case results of LDT compared to alternative debridement therapies on the costeffectiveness plane. - 4,000-3,500 Increasing the rate of clinical intervention over - 4,000 time for undebrided wounds across all therapies (month 1 to 5: 1%, 2%, 10%, 25% and 50% for honey/ hydrogel; 0.5%, 1%, 5%, 10%, and 25% for all other therapies) made little difference to the incremental results and no difference to the cost-effectiveness conclusions of the base case. When the same rates were assumed across all therapies (month 1 to 5: 0.5%, 1%, 5%, 10% and 25% for all other therapies), LDT was no longer dominant compared to hydrogel. Although estimated to provide higher QALYs in these scenarios, LDT was predicted to be more expensive compared to hydrogel. Nevertheless, with an ICER of 14,802 per QALY gained, LDT would still be considered to be cost-effective at a threshold of 20,000 per QALY. Infection and adverse event rates Scenarios were tested in which the infection rate associated with surgical-type therapies was applied per month of treatment, rather than per procedure as in the base case; however, these rates were not found to be drivers of results. Due to the relatively low incidence of adverse events associated with debridement therapies, and their low cost and utility consequences, adverse events where not found to be a driver of results. Other sensitivity analysis A range of further sensitivity analyses were conducted as presented in Table 4. Figure 3 presents the results of the sensitivity analysis in the form of tornado plots for mechanical, hydrogel and honey the debridement methods closest to LDT in the base Wounds UK LDT: An economic, scientific and clinical evaluation Nov (4) Suppl 8

56 EVIDENCE-BASED PRACTICE case results and also for surgical debridement. The cost of LDT and the probability of its success in achieving debridement were found to be the key cost drivers, while the utilities associated with LDT and its comparator were key drivers of accumulated benefits. DISCUSSION This is the first attempt we are aware of to estimate the cost-effectiveness of multiple options for debridement against a common comparator LDT. Under the majority of scenarios modelled, LDT was estimated to be a cost-effective therapy for wound debridement. The base case results suggest that initiating treatment with LDT may be a dominant intervention compared to hydrogel, honey, mechanical, surgical, sharp, and hydrosurgical debridement methods. That is, adopting the use of LDT may result in both cost savings and greater benefits for a patient over one year. All debridement methods appear to be similar in terms of overall quality of life impact for patients, partially attributable to the assumed practice of changes in treatment for undebrided wounds; however, there appears to be a meaningful estimated difference in costs between treatments. LDT is estimated to be cost saving compared to surgicaltype therapies in the base case analysis and also the majority of sensitivity analyses performed. The costs accumulated over one year were more closely Table 4: Results of univariate sensitivity analyses Variable changed LDT vs. surgical LDT vs. sharp LDT vs. hydrosurgical LDT vs. mechanical LDT vs. hydrogel LDT vs. honey Rates Probability of debridement with LDT (69% to 84%)^ Dominant Dominant Dominant 29,307/ QALY 358,373/ QALY 43,564/ QALY Dominant Dominant Dominant Probability of infection (+/- 10% of mean) Dominant Dominant Dominant Dominant Dominant Dominant Probability of AEs (+/- 10% of mean) Dominant Dominant Dominant Dominant Dominant Dominant Costs LDT cost per bag ( 195 to 295) Dominant Dominant Dominant Dominant Dominant Dominant C-E Dominated Clinical intervention* ( 3,174 to 12,418.50) Dominant Dominant Dominant Dominant 20,182/ QALY Dominant Dominant Infection** ( 1,268) Dominant Dominant Dominant Dominant Dominant Dominant All costs (+/- 10% of mean) Dominant Dominant Dominant Dominant Dominant Dominant Utilities Baseline utility (+/- 5% of mean) Dominant Dominant C-E Dominant Dominant Dominant Dominant During LDT therapy (+/- 10% of mean) Dominant Dominant Dominant Dominant Dominant Dominant C-E C-E C-E 7,214/QALY C-E During comparator therapy [only]^^ C-E C-E C-E Dominant 16,061/ QALY C-E Dominant Dominant Dominant Dominant Dominant *across all therapies, ^ up/down 10% of base case value, *all toe amputation versus all leg amputation,**nhs reference costs with CC (base case used cost without CC) ^^bounds of 95% CI tested if available, else ± 10% of base case value capped at baseline. 10% lead to greater extremes than those CIs available. C-E: cost-effective at threshold of 20,000/QALY 9 Wounds UK LDT: An economic, scientific and clinical evaluation Nov (4) Suppl

57 EVIDENCE-BASED PRACTICE % LDT debridement LDT cost per bag Cost of infection All cost Cost of amputation Probability of infection Probability of AEs % LDT debridement LDT cost per bag Cost of amputation Cost of infection All cost Probability of infection Probability of AEs % LDT debridement LDT cost per bag Cost of amputation All cost Cost of infection Probability of infection Probability of AEs All cost % LDT debridement LDT cost per bag Cost of infection Cost of amputation Probability of infection Probability of AEs Incremental Costs (LDT vs. Mechanical) Incremental Costs (LDT vs. Hydrogel) Incremental Costs (LDT vs. Honey) - 4,000-3,800-3,600-3,400-3,200-3,000 Incremental Costs (LDT vs. Surgical) During LDT therapy During comparator therapy Baseline utility % LDT debridement Probability of infection During comparator therapy During LDT therapy Baseline utility % LDT debridement Probability of infection During comparator therapy During LDT therapy Baseline utility % LDT debridement Probability of infection During comparator therapy During LDT therapy Baseline utility % LDT debridement Probability of infection Incremental Costs (LDT vs. Mechanical) Incremental Costs (LDT vs. Hydrogel) Incremental Costs (LDT vs. Honey) Incremental Costs (LDT vs. Surgical) Figure 3: Tornado plots sensitivity analyses for LDT vs. mechanical, hydrogel, honey and surgical debridement therapies. AE = adverse event. comparable when initiating treatment with LDT and the other non-surgical therapies; however, LDT was estimated to be cost saving in the base case and in many cases tested in sensitivity analyses. To address the uncertainty around our results, we undertook a sensitivity analysis, which highlights the parameter inputs that are most influential for overall costs and outcomes. It is particularly important to have strong evidence for the chosen values of these influential parameters. The sensitivity analysis conducted showed that the cost of LDT and the probability of its success in achieving debridement were the key cost drivers, while the utility values associated with the debridement interventions were key drivers of accumulated benefits, emphasising the importance of robust quality of life evidence in this area. The cost of treatment was a significant driver for surgical therapies due to their higher cost compared to the other debridement therapies considered. In undertaking this research we faced a number of challenges relating to the variation in wound presentation and care in clinical practice and the lack of comparative data based on good quality RCTs of the available interventions. Despite the heterogeneity of patients, complexity of debridement approaches and variation in wound care pathways observed in clinical practice, the model developed for this analysis was necessarily simple. In reality, treatment may be tailored to the type of wound presented and its progression; in such cases, changes in debridement therapy may happen over different time intervals and some debridement methods more frequently follow others. For example, one debridement method may be used for a short time to rid the wound of most sloughy tissue Wounds UK LDT: An economic, scientific and clinical evaluation Nov (4) Suppl 10

58 EVIDENCE-BASED PRACTICE (surgical) or soften hard eschar (autolytic), followed by another debridement therapy, such as LDT, for a longer period of time. Our simple model gives an overall picture of the comparative cost-effectiveness of therapies in circumstances where any of the available debridement methods would be clinically appropriate. An additional issue is that published data available in this area is limited, which alters both the level of complexity that can be accommodated in modelling and the reliability of any results modelling can provide. The consequent reliance on expert opinion to inform data inputs and modelling assumptions is a major limitation of the modelling described here. Further limitations as a result of data paucity include possible issues concerning consistency of studies from which parameter values were derived, choice of modelled endpoint and type of wound modelled. The primary endpoint modelled was wound debridement; however, modelling the treatment of wounds until healing, including any recurrences, would be superior. No distinction could be made between wound types, despite known differences between diabetic foot or venous leg ulcers. The described data limitations and structural assumptions lead to great uncertainty in the modelling results; however, it was difficult to quantify the impact of this uncertainty through probabilistic sensitivity analysis due to the paucity of data to support the specification of sampling distributions and reasonable ranges for parameter values. Full probabilistic sensitivity analysis is strongly recommended should sufficient data become available in the future. CONCLUSIONS Despite its limitations the model provides useful information regarding the cost-effectiveness of LDT and important insights for both healthcare professionals and budget holders regarding the influential factors associated with treatment that determine the cost-effectiveness of debridement therapy. The modelling process has enabled the identification and specification of gaps in available evidence relating to wound debridement. Our findings suggest that undertaking further research to improve this evidence base, particularly in the areas of quality of life and resource use associated with therapies, is of great importance if the costs and effects of wound debridement are to be better understood and to support evidence-based decision making. Acknowledgements We would like to thank our clinical experts for their guidance as we undertook this research: Professor Keith Harding, Wound Healing Research Centre, Cardiff University Julie Evans, Tissue Viability Nurse and Rosalyn Thomas, Deputy Head of Podiatry, Abertawe Bro Morgannwg University Health Board, Swansea. Declaration of interests All authors declare that the Swansea Centre for Health Economics at Swansea University was given financial support from BioMonde Ltd, a company that manufacturers larval debridement therapies. This support was in the form of an unrestricted research grant that enabled the research reported here. Professor Ceri Phillips is the Research Director of the Wales Wound Care Innovation Centre. REFERENCES Caputo WJ, Defede JL, Simm L, Dharma H (2008). A prospective randomised controlled clinical trial comparing hydrosurgery debridement with conventional surgical debridement in lower extremity ulcers. Int Wound J 5; Dumville JC, Worthy G, Soares MO, B et al (2009). VenUS II: a randomised controlled trial of larval therapy in the management of leg ulcers. Health Technol Assess 13: Gethin G, Cowman C (2009). Manuka honey vs. hydrogel a prospective, open label, multicentre, randomised controlled trial to compare desloughing efficacy and healing outcomes in venous ulcers. J Clin Nurs 18(3); Granick MS, Jacoby M, Noruthun S, et al (2006). Efficacy and costeffectiveness of a high-powered parallel waterjet for wound debridement. Wound Repair Regen 14(4); Hall S (2010). A review of maggot debridement therapy to treat chronic wounds. Br J Nurs 19(15); S26; S Iglesias CP, Cullum N, Torgerson DJ; Venus I Collaborators (2004). Economic analysis of VenUS I, a randomized trial of two bandages for treating venous leg ulcers. Br J Surg 91(10); Mosti GIM, Picerni P, Magliaro A, Mattaliano V (2005). The debridement of hard to heal leg ulcers by means of a new device based on Fluidjet technology. Int Wound J 2(4); Nelson EA, Craig D, Iglesias C, et al (2006). A series of systematic reviews to inform a decision analysis for sampling and treating infected diabetic foot ulcers. Health Technol Assess 10(12); iii-iv, ix-x, OECD 2010/11. PPP Indices Posnett J, Franks PJ (2007). The costs of skin breakdown and ulceration in the UK. Skin Breakdown: The Silent Epidemic. The Smith and Nephew Foundation. Ribu LBK, Hanestad BR, Moum T, Rustoen T (2008). A longitudinal study of patients with diabetes and foot ulcers and their health-related quality of life: wound healing and quality-of-life changes. J Diabetes Comp 22(6); Soares MO, Bland JM, Cullum N, et al (2009). Cost effectiveness analysis of larval therapy for leg ulcers. BMJ (Clin Res Ed) 338; b825. Watson JM, Soares MO, Chuang LH, et al; Venus III Team (2011). VenUS III: a randomised controlled trial of therapeutic ultrasound in the management of venous leg ulcers. Health Technol Assess 15(13); Wounds UK LDT: An economic, scientific and clinical evaluation Nov (4) Suppl

59 EVIDENCE-BASED PRACTICE Evidence for larval debridement therapy in wound cleansing and healing Larvae of the medicinal maggot (Lucilia sericata) are now used worldwide to treat and manage chronic wounds, such as leg ulcers, pressure ulcers, diabetic foot ulcers, as well as for infected surgical wounds, burns and trauma injuries. Clinical evidence suggests that larval debridement therapy (LDT) has the following beneficial effects on a wound: debridement, cleansing and enhanced healing. Scientific studies reveal some of the mechanisms behind larval action: larval enzymes are responsible for breaking down and removing necrotic tissue in the wound bed; antibacterial factors present in secretions inhibit wound bacteria and disrupt biofilm; and distinct compounds within secretions appear to promote important physiological processes involved in wound healing, such as fibroblast migration and angiogenesis. This article summarises the most recent scientific evidence, which seeks to explain the actions of LDT in chronic and infected wounds. KEY WORDS Larval therapy Debridement Biofilm Wound healing ROLE OF LDT IN WOUND DEBRIDEMENT Of all the actions associated with LDT, tissue debridement is the best understood. Verified by copious clinical studies (Sherman, 2003; Chan et al, 2007; Tantawi et al, 2007; Gilead et al, 2012), randomised controlled trials (RCTs) (Dumville et al, 2009; Opletalová et al, 2012), and rigorous scientific evidence (Chambers et al, 2003; Telford et al, 2010; Britland et al, 2011), it is widely acknowledged that larvae can selectively dissolve necrotic tissue. Deep tissue debridement is also possible because larvae are able to access nooks and crannies of wounds (Zumpt 1965), and may lead to more rapid debris removal rates compared to many other non-surgical treatments (Whitaker et al, 2007). The largest component of normal skin is the extracellular matrix (ECM), which acts as a structural scaffold for cells. The breakdown of ECM components of a wound by proteolytic enzymes is an intrinsic part of the initial stages of tissue repair (Gailit and Clark, 1994). Larvae have been shown to secrete a mixture of enzymes (Figure 1) including chymotrypsin and trypsinlike, aspartyl and metalloproteinases (Chambers et al, 2003), which break down fibrin clots and necrotic tissue, and promote the reorganisation and modification of ECM (Horobin et al, 2006) Larvae provide their own optimal conditions for serine and metalloproteinases to act within the wound and they secrete ammonia to increase the ph in the wound bed to activate trypsin-like proteases. Proteolytic enzymes, such as chymotrypsin, have been shown to be the key agents responsible for the debriding action of larvae. Recently, researchers have produced a recombinant chymotrypsin I, with very potent enzymatic activity (Telford et al, 2010). A study involving patients with venous leg ulcers showed how this active recombinant enzyme improved eschar breakdown in these wounds compared to that seen with human and bovine chymotrypsins (Telford et al, 2010). Although its role in wound debridement is unequivocally established, chymotrypsin present in larval secretions has also recently been identified as an influential molecule in preventing the adherence of pathogenic bacteria to potential colonisation sites in the wound bed, as well as being important in the formation and disruption of wound biofilm. ROLE OF LDT IN INFECTION CONTROL/ BIOFILM MANAGEMENT Antibacterial effects of larval secretions The ability of larvae to combat wound infections has been widely reported. This may be simply due to rapid debridement or ingestion and subsequent destruction of wound pathogens as larvae feed (Mumcuoglu et al, 2001; Daeschlein et al, 2007). Nonetheless, researchers Figure 1: Larvae of Lucilia sericata, secreting enzymes as they feed. DR YAMNI NIGAM, Associate Professor (Biomedical Science) College of Human and Health Sciences Swansea University, UK Wounds UK LDT: An economic, scientific and clinical evaluation Nov (4) Suppl 12

60 EVIDENCE-BASED PRACTICE KEY POINTS LDT can be used for the rapid removal of necrotic and non-viable tissue in the wound bed. Larval secretions contain effective antibacterial agents with potent activity against Gram-negative and -positive bacteria. LDT has been shown to interfere with bacterial biofilm formation and establishment. LDT secretions may help to stimulate physiological processes involved in wound healing. Figure 2: Collection of sterile Lucilia sericata externalised secretions. have long been convinced that larval secretions also contain effective antibacterial agents (Simmons, 1935a,b; Pavillard and Wright, 1957). Subsequently, recent studies have provided profound evidence of the presence of antibacterial factors within larval secretions (Bexfield et al, 2004; Kerridge et al, 2005; Barnes et al, 2010), confirming potent activity against both Gram-positive and Gram-negative bacteria (Huberman et al, 2007; Jaklic et al, 2008). Several recent studies have shed new light on the actual nature of these antibacterial factors. For example, a large (high molecular weight) peptide, Lucifensin, has been purified from larval secretions and various tissues (Cerevosky et al, 2010). Lucifensin has been shown to be potently active against several bacteria including S. pyogenes and S. pneumoniae (Andersen et al, 2010). Additionally, fractions collected from sterile larval secretions (Figure 2), showed powerful activity against 12 out of 15 tested clinical isolates of meticillin-resistant S. aureus (MRSA) (Figure 3), as well as a range of other isolated pathogens (Bexfield et al, 2008). Moreover, the mass and empirical formula of a small, low molecular weight antibacterial agent present in these fractions has been accurately determined, and registered as a new, novel antibiotic, Seraticin (Nigam et al, 2010). A further investigation on antibacterial activities of compounds released externally by the larvae has confirmed the presence of a range of structurally diverse compounds (Kruglikova and Chernysh, 2011), and most recently, research scientists in China have reported the isolation and purification of yet another antibacterial molecule, MAMP, from larval secretions, which has a significant inhibitory effect on S. aureus and appears to work by disrupting the bacterial cell membrane (Zhang et al, 2013). The cumulative scientific evidence outlined above undisputedly suggests the presence of antibacterial activity in larval secretions. How the secretion of these externalised factors manifests clinically, and to what extent it influences wound cleansing, still needs to be thoroughly investigated. To this end, several studies report on the inducible nature of larval antibacterial activity. Huberman et al (2007) reported a three- to six-fold increase in the comparable antibacterial activity in larvae removed from chronic wounds, compared to sterile larvae. Kabawata et al (2010) analysed the influence of pre-incubating sterile larvae in a bacterial suspension, and subsequently assessed larval extracts for antibacterial activity. The results showed that infected larvae had better antibacterial capacities than sterile larvae. The researchers argue that the clinical wound situation would enable larvae in the infected environment to influence production of antibacterial activities. This discovery suggests that sterile larvae placed in an infected wound are triggered by the presence, or oral ingestion, of surrounding bacteria, and start producing and secreting their antibacterial agents, acting like small, antibiotic-secreting factories. Anti-biofilm effects of larval secretions Often, wound bacteria aggregate to form a resistant layer called a biofilm. This is an established community of stable microbial cells that adhere to each other and/ or to a surface, and are embedded in a complex selfproduced mixture of extracellular polymers. It is generally agreed that wound chronicity is aggravated by the presence of a biofilm. Wound biofilm is extremely difficult to eradicate; many topical treatments are ineffective, and antibiotics, designed to attack free (planktonic) bacterial cells cannot penetrate this walled community (Davies et al, 2007; Cowan et al, 2013). It has been shown that larval secretions can both disrupt established biofilm and prevent its formation (van der Plas et al, 2008; Harris et al, 2009). Harris and coworkers (2009) considered the effect of larval secretions on the formation and disruption of biofilms from two different strains of S. epidermidis, 1457 and 5179-R1, which exhibit different mechanisms of biofilm formation. Both types of biofilm formation were disrupted by the larvae, and it was shown that chymotrypsin, derived from larval secretions, was the responsible molecule. This Bacterial growth (%) MR108 JCSC 1968 N315 EMRSA-13 85/2082 JCSC 1978 NCTC EMRSA-16 COL EMRSA MVV2 Control Figure 3: Growth inhibition effect of larval secretions (<500Da fraction) on 12 clinical isolates of MRSA (bacterial susceptibility was assessed using the Turbidometric assay). 13 Wounds UK LDT: An economic, scientific and clinical evaluation Nov (4) Suppl

61 EVIDENCE-BASED PRACTICE detrimental effect on biofilm was observed for both nascent and pre-formed biofilms of S. epidermidis R1 (Harris et al, 2013). Chymotrypsin has also recently been implicated in the destruction of important molecules in the necrotic wound bed (macromolecules (MSCRAMM), which may act as adherent sites for the colonisation and subsequent infection of pathogenic bacteria (Pritchard and Brown, 2013). By removing these bacterial mooring sites, larvae applied to a wound may help in preventing further wound infections. Furthermore, it has recently been established that larval secretions contain an enzyme that is able to break down DNA from wound slough (Brown et al 2012). This DNAse is also able to digest bacterial DNA a significant discovery because extracellular DNA is an important requirement for some bacterial species to instigate biofilm formation. If DNAse present in larval secretions eliminates this source, this may explain the anti-biofilm effects of larvae and their secretions. Interestingly, like the antibacterial molecules previously mentioned, larval molecules associated with disruption of biofilm have also been shown to be inducible, eg secretions collected from larvae incubated with bacteria were more able to destroy P. aeruginosa biofilm (Jiang et al, 2012) Other studies have considered the effects of larvae on biofilm production on surfaces commonly used in a medical setting (Cazander et al, 2009; 2010). Larval secretions were found to be able to prevent biofilm formation and disrupt existing biofilms of P. aeruginosa; the study, which encompassed many different bacterial species, noted reduced biofilm formations after treatment with larval secretions on polyethylene, titanium and stainless steel surfaces, with a maximal reduction in biofilm formation of 92%. This result may be of great significance, especially when considering peri-prosthetic infections. Combining larval secretions with existing medical treatments may also possess greater therapeutic potential, and this has been initially investigated with antibiotics. It was shown that combining larval secretions with either vancomycin or daptomycin, increased potency of the antibiotic (van der Plas et al, 2010). It seems highly probable, therefore, that in a wound, larvae secrete distinct factors that are able to combat wound pathogens and also interfere with bacterial biofilm formation and establishment. ROLE OF LDT AND EXUDATE MANAGEMENT Wound exudate is the fluid produced by wounds following haemostasis. The inflammatory response, which is mounted on tissue injury, increases capillary permeability. This lets large, important immune cells out of capillaries and into the wound site and leads to fluid leakage in the vicinity of the wound. Normally, wound exudate is a healthy sign, containing many growth factors and molecules that stimulate the healing process. However, if the wound becomes chronic, the inflammatory phase is prolonged. Excessive exudate, usually consisting of pathogenic bacteria and destructive proteolytic enzymes, may build up and cause a host of problems, including malodour, skin maceration and a delay in healing (Hampton and Collins, 2004). Since LDT removes dead and damaged tissue, which eases the microbial burden of the wound, it follows that LDT could facilitate the reduction of the inflammatory response. This would in turn stabilise the moisture balance and combat excessive exudation (Schultz et al, 2003). However, contradictory reports suggest that LDT may increase wound exudate (Vuolo, 2004). Thus the role of larvae in managing wound exudate has not yet been unequivocally established. EFFECT OF LARVAL SECRETIONS ON WOUND HEALING During wound healing, specialised leukocytes produce a wide variety of immune mediators, growth factors and distinctive cytokines. After removal of necrotic and infected tissue, the wound progresses into the proliferative phase. Granulation occurs and fibroblasts migrate inwards from the wound margins to generate and assemble collagen. Several researchers have shown the positive effects of larval secretions on fibroblasts and other cells involved in facilitating healing (Prete, 1997; van der Plas et al, 2007). Recently, proteolytic larval secretions were found to induce changes in cell morphologies and to stimulate fibroblast migration in the wound (Horobin et al, 2003). Fibroblasts are stimulated by many chemical activators and messengers, mostly released by macrophages, which dominate the clinical picture towards the end of the inflammatory phase. Fibroblasts secrete a variety of cytokines, allowing other vital cells, eg endothelial cells and angiocytes, to proliferate. Expansion of these cell numbers contributes to the Wounds UK LDT: An economic, scientific and clinical evaluation Nov (4) Suppl 14

62 EVIDENCE-BASED PRACTICE growth of new blood vessels (angiogenesis), allowing oxygen to reach newly forming tissue. The effect of larval secretions on inflammatory cells has been studied. Neutrophils, monocytes and macrophages are present in excess in chronic wounds. They produce increased amounts of pro-inflammatory cytokines, proteases, eg elastase, and reactive oxygen species (ROS) such as hydrogen peroxide, and are therefore extremely damaging to the chronic wound environment (Schreml et al, 2010). Investigations into the effect of larval secretions on neutrophil activity and viability revealed that secretions are capable of inhibiting elastase release and hydrogen peroxide production in activated neutrophils, without compromising neutrophil viability (van der Plas et al, 2007). Also, there was decreased production of pro-inflammatory cytokines and macrophage inflammatory protein, with increased production of anti-inflammatory cytokines (van der Plas et al, 2009a). This research further demonstrates the capacity of larvae to reduce inflammation in a chronic wound. For wounds to progress to healing and closure, the inward migration of resident epidermal keratinocytes and dermal cells, including dermal microvascular cells, is a crucial step. In a scratch test comparing larval secretions to secretion-free controls, larval secretions were found to significantly induce migration of human microvascular endothelial cells (HMEC1) and the presence of secretions increased wound healing by 30% (Wang et al, 2009). The authors also showed that a key signalling pathway was activated by larval secretions, and this encouraged the endothelial cell migration. Distinct pro-angiogenic compounds have also been detected within larval secretions, including the amino acids L-histidine, 3-guanidinopropionic acid (GPA) and L-valinol (Bexfield et al, 2009). All three identified compounds, but notably valinol, were found to specifically and significantly enhance the proliferation of human endothelial cells, with no effect observed on fibroblast proliferation. In other research, fatty acids from homogenised larvae have also been shown to enhance angiogenesis of dermal excision wounds via increased protein expression of an angiogenic growth factor, VEGF (vascular endothelial growth factor) (Zhang et al, 2010). Finally, there is experimental evidence to suggest that larval secretions may exert an effect on another important component of the immune response the complement system. This complex cascade of potent proteins is normally systemically activated to crush an invading pathogen attack, so is a necessary accompaniment to a healthy and protective immune state. However, excessive local complement activation around the wound environment can lead to chronic inflammation. Researchers have recently shown that larval secretions suppress complement activity by inhibiting the production of several important complement proteins. They concluded that the ability of larvae to reduce this overactive immune response may play an important role in wound healing (Cazander et al, 2012). CONCLUSION The studies outlined above, undertaken in the laboratories of independent scientists, demonstrate a sound scientific basis for the wound debriding, cleansing and healing effects observed during larval therapy. Larval proteolytic enzymes encourage wound debridement, secreted antibacterial factors kill a range of pathogens and are capable of disrupting biofilm. Larvae can steer wound healing by directing it away from a chronic inflammatory response through the attenuation of neutrophils, monocytes and macrophages. Their secretions promote fibroblast migration, while pro-angiogenic activity of secretions actively encourages granulation tissue formation. In the last decade, research scientists have avidly raised their game revealing the presence of distinct bio-active molecules produced by larvae. This has led to a much better understanding of the scientific mechanisms that underlie the actions clinically observed in the wounds with the presence of larvae. Clearly, the action of larvae in wounds is multifaceted and, undoubtedly, further research will reveal yet more fascinating interactions between the molecules they produce and the promotion of a healthy wound bed. REFERENCES Andersen AS, Sandvang D, Schnorr KM, et al (2010). A novel approach to the antimicrobial activity of maggot debridement therapy. J Antimicrob Chemother 65: Barnes KM, Gennard DE, Dixon RA (2010). An assessment of the antibacterial activity in larval excretion/secretion of four species of insects recorded in association with corpses, using Lucilia sericata Meigen as the marker species. Bull Entomol Res 22: 1 6 Bexfield A, Nigam Y, Thomas S, Ratcliffe NA (2004). Detection and partial characterisation of two antibacterial factors from the excretions/ secretions of the medicinal maggot Lucilia sericata and their activity against methicillin-resistant Staphylococcus aureus (MRSA). Microbes Infect 6: Bexfield A, Bond AE, Roberts EC, et al (2008). The antibacterial activity against MRSA strains and other bacteria of a <500 Da fraction 15 Wounds UK LDT: An economic, scientific and clinical evaluation Nov (4) Suppl

63 EVIDENCE-BASED PRACTICE from maggot excretions/secretions of Lucilia sericata (Diptera: Calliphoridae). Microbes Infect 10: Bexfield A, Bond AE, Morgan C, et al. (2009). Amino acid derivatives from Lucilia sericata excretions/secretions may contribute to the beneficial effects of maggots therapy via increased angiogenesis. Br J Dermatol 162: Britland ST, Smith AG, Finter WF, et al (2011) Recombinant Lucilia Sericata chymotrypsin in a topical hydrogel formulation degrades human wound eschar ex vivo. Biotechnol Prog 27(3); Brown A, Horobin A, Blount DG, et al. (2012). Blow fly Lucilia sericata nuclease digests DNA associated with wound slough/eschar and with Pseudomonas aeruginosa biofilm Medical and Veterinary Entomol 26: Cazander G, van Veen KE, Bouwman LH, et al (2009). The influence of maggot excretions on PAO1 biofilm formation on different biomaterials. Clin Orthop Relat Res 467: Cazander G, van de Veerdonk MC, Vandenbroucke-Grauls CM, et al (2010). 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Skin Pharmacol Physiol 20: Davies SC, Ricotti C, Cazzaniga, A, et al (2007). Microscopic and physiologic evidence for biofilm-associated wound colonization in vivo. Wound Rep Regen 16: Dumville JC, Worthy G, Bland JM, et al (2009). Larval therapy for leg ulcers (VenUS II): randomised controlled trial. BMJ 338: Gailit J, Clark RAF (1994) Wound repair in the context of the extracellular matrix. Curr Opin Cell Biol 6: Hampton S, Collins F (2004) Holistic wound assessment. In: Hampton S, Collins F, eds. Tissue Viability. Whurr Publications, London: Harris LG, Bexfield A, Nigam Y, et al (2009) Disruption of S.epidermidis biofilms by medicinal maggot Lucilia sericata excretions/secretions. Int J Artif Organs 32: Harris L, Nigam Y, Sawyer J, et al (2013) Lucilia sericata chymotrypsin disrupts protein adhesin-mediated staphylococcal biofilm formation. App Envir Microbiol 79: Horobin AJ, Shakesheff KM, Woodrow S, et al (2003) Maggots and wound healing: an investigation of the effects of secretions from Lucilia sericata larvae upon interactions between human dermal fibroblasts and extracellular matrix components. Br J Dermatol 148: Horobin AJ, Shakesheff KM, Pritchard DI (2006) Promotion of human dermal fibroblast migration, matrix remodelling and modification of fibroblast morphology within a novel 3D model by Lucilia sericata larval secretions. J Invest Dermatol 126: Huberman L, Gollop N, Mumcuoglu KY, et al (2007) Antibacterial properties of whole body extracts and haemolymph of Lucilia sericata maggots. J Wound Care 16: Jaklic D, Lapanje A, Zupancic K, et al. (2008) Selective antimicrobial activity of maggots against pathogenic bacteria. J Med Microbiol 57: Jiang K-C, Sun X-J, Wang W, et al (2012) Excretions/secretions from bacteriapretreated maggot are more effective against Pseudomonas aeruginosa biofilms. PLoS ONE 7(11): e doi: Kawabata T, Mitsui H, Yokota K, et al (2010). Induction of antibacterial activity in larvae of the blowfly Lucilia sericata by an infected environment. Med Vet Entomol 24: Kerridge A, Lappin-Scott H, Stevens JR (2005) Antibacterial properties of larval secretions of the blowfly, Lucilia sericata. Med Vet Entomol 19 : Kruglikova AA, Chernysh SI (2011) Antimicrobial compounds from the excretions of surgical maggots, Lucilia sericata (Meigen) (Diptera, Calliphoridae). Entomol Rev 91: Mumcuoglu KY, Miller J, Mumcuoglu M, et al (2001) Destruction of bacteria in the digestive tract of the maggot of Lucilia sericata (Diptera: Calliphoridae). J Med Entomol 38: Gilead L, Mumcuoglu KY, Ingber A (2012) The use of maggot debridement therapy in the treatment of chronic wounds in hospitalised and ambulatory patients. J Wound Care 21(2): Nigam Y, Dudley E, Bexfield A, et al (2010).The physiology of wound healing by the medicinal maggot, Lucilia sericata. Adv Insect Physiol 39: Opletalová K, Blaizot X, Mourgeon B, et al (2012) Maggot therapy for wound debridement. A randomized multicentre trial. Arch Dermatol 148: Pavillard ER, Wright EA (1957). An antibiotic from maggots. Nature 180, Prete PE (1997) Growth effects of Phaenicia sericata larval extracts on fibroblasts: Life Sci 60: Pritchard DI, Brown AP (2013) Degradation of MSCRAMM target macromolecules in VLU slough by Lucilia sericata chymotrypsin 1 (ISP) persists in the presence of tissue gelatinase activity. Int Wound J [Epub ahead of print]. Schreml S, Szeimies RM, Prantl L, et al (2010) Oxygen in chronic wound healing. Br J Dermatol 163(2): Schultz GS, Sibbald G, Falanga V, et al (2003). Wound bed preparation: a systematic approach to wound management. Wound Rep Regen 11: S1 S27. Sherman RA (2003) Maggot therapy for treating diabetic foot ulcers unresponsive to conventional therapy. Diabetes Care 26: Simmons S (1935a) A bacteriocidal principle in excretions surgical maggots which destroys important etiological agents of pyrogenic infections. J Bacteriol 30: Simmons S (1935b) The bactericidal properties of excretions of the maggot of Lucilia sericata. Bull Entomol Res 26: Tantawi TI, Gohar YM, Kotb MM, et al (2007) Clinical and microbiological efficacy of MDT in the treatment of diabetic foot ulcers. J Wound Care 16: Telford Microbes Infect G, Brown AP, Seabra RAM, et al (2010) Degradation of eschar from venous leg ulcers using a recombinant chymotrypsin from Lucilia sericata. Br J Dermatol 163: van der Plas MJA, ven der Does AM, Baldry M, et al (2007) Maggot excretions/secretions inhibit multiple neutrophil pro-inflammatory responses. 9: van der Plas MJ, Jukema GN, Wai SW, et al (2008) Maggot excretions/ secretions are differentially effective against biofilms of Staphylococcus aureus and Pseudomonas aeruginosa. J Antimicrob Chemother 61: van der Plas MJA, Baldry M, Van Dissel JT, et al (2009) Maggot secretions suppress pro-inflammatory responses of human monocytes through elevation of cyclic AMP. Diabetologia 52: van der Plas MJ, Dambrot C, Dogterom-Ballering HC, et al (2010) Combinations of maggot excretions/secretions and antibiotics are effective against Staphylococcus aureus biofilms and the bacteria derived therefrom. J Antimicrob Chemother 65: Vuolo J (2004) Current options for managing the problem of excess wound exudate. Professional Nurse 19: 9, Wang SY, Wang K, Xin Y, DC (2009) Maggot excretions/secretions induces human microvascular endothelial cell migration through AKT1. Mol Biol Rep 37: Whitaker IS, Twine C, Whitaker MJ, et al. (2007) Larval therapy from antiquity to the present day: mechanisms of action, clinical applications and future potential. Postgrad Med J 83: Zhang Z, Wang S, Diao Y, et al (2010) Fatty acid extracts from: Lucilia sericata larvae promote murine cutaneous wound healing by angiogenic activity. Lipids Health Dis 9: 24. Doi: / x Zhang Z, Wang J, Zhang B, et al (2013) Activity of antibacterial protein from maggots against Staphylococcus aureus in vitro and in vivo. Int J Mol Med 31: Zumpt F (1965) Myiasis in Man and Animals in the Old World. Butterworths: London, UK. Wounds UK LDT: An economic, scientific and clinical evaluation Nov (4) Suppl 16

64 EVIDENCE-BASED PRACTICE Setting up a LDT service: lessons learnt from Blackpool KEY WORDS Service provision Multdisciplinary team Changing practice A larval debridement service at the Blackpool Teaching Hospitals was set up in 2011 to extend the debridement options for patients attending the vascular outpatient clinic. A treatment protocol was implemented to facilitate larval debridement therapy (LDT) and this was subsequently adapted to involve the community teams working in the Blackpool area. Two years on, LDT is now an established debridement method with good integration between the hospital and community teams delivering the service. VITTORIO PERRICONE, Consultant Surgeon, Vascular Surgery, Blackpool Victoria Hospital PATRICIA VICKERS, Tissue Viability Nurse Advisor, Blackpool Victoria Hospital JAN BAMBER, Non-Medical Prescribing Lead, Blackpool Teaching Hospitals NHS Foundation Trust JENNIFER LOMAX, Pharmacist, Blackpool Victoria Hospital TRACY CHANDLER Nurse, Surgical Assessment Unit, Blackpool Victorial Hospital INTRODUCING A LDT SERVICE Larval debridement therapy (LDT) was introduced by the vascular team at the Blackpool Teaching Hospitals in September The initial intention was to target patients who were unfit for surgical intervention, but would benefit from a lower-risk debridement option. This was subsequently expanded to include patients who met the criteria for surgical debridement, but for whom LDT was seen as a cheaper, but equally effective, treatment. A protocol was agreed that allowed efficient and timely delivery of LDT with measurement and ordering of larvae by the staff within the surgical assessment unit (SAU). This treatment protocol involved the following referral and treatment steps: Patient was assessed by the vascular consultant in the outpatient clinic. If the criteria for LDT were met and the patient consented to treatment, they would be referred to SAU for wound measurement and ordering of the larvae Patient was seen next day in SAU for application of the larvae. Patient information on LDT was provided to improve concordance with treatment and the patient given a carrier bag with appropriate outer dressings to take home Patient was seen by the district nurses for daily wound care (eg to check/change outer dressing) in accordance with manufacturer s recommendations Patient was seen after four days in the vascular clinic for review and/or reapplication of LDT. A key goal in setting up this service was to minimise the need for a hospital stay, helping to reduce costs and benefiting patients. However, problems due to lack of an appropriate treatment space in the SAU due to changes within the hospital, meant an alternative pathway was needed with greater involvement of the community teams. This led to the current system in which the patients are referred by the vascular team to the hospital trust s tissue viability nurse (TVN) advisor. After assessment in the outpatient vascular clinic, a patient s details are sent by letter/ to the TVN advisor, which are then communicated to the appropriate community team. Advice on measurement and ordering of larvae is given via telephone or by visit from the TVN advisor for more complex wounds. This protocol is now well-established with the TVN advisor acting as a coordinator for LDT. The development of the LDT service has required good communication between the hospital and community teams to ensure effective coordination of personnel and timely ordering/application and removal of larvae. In addition, education of GPs and district nurses has been important in expanding this service to the community with training and support provided on application and removal of the larvae. The use of LDT on surgical wards has also been encouraged within the hospital. Again, this was initially targeted at patients who required wound debridement but were not fit for surgery. Concerns among healthcare staff with regards to the use of larval therapy, largely due to the yuck factor, had meant that LDT was not established as a method of debridement. Larval therapy was also seen as a complicated technique to perform. However, education and support of link nurses has led to greater acceptance of the therapy and uptake on wards, including orthopaedics, where LDT is used 17 Wounds UK LDT: An economic, scientific and clinical evaluation Nov (4) Suppl

65 EVIDENCE-BASED PRACTICE for patients with non-healing chronic wounds or large haematomas. With greater awareness, has come increased confidence in using LDT, with areas more likely to discuss cases with the TVN advisor and be proactive in prescribing LDT. To help overcome initial procurement issues, prescribing procedures within the hospital have been simplified, with all prescriptions now authorised on a named patient basis by the vascular surgeon using a standard form and verified by the hospital pharmacist. This has improved the ordering process, with more timely application of larvae and the ability to document overall usage within the hospital. Over the past 16 months (April 2012 to August 2013), there have been a total of 29 prescriptions for LDT in the community (Blackpool and North Lancashire) with an average of 1.8 prescriptions per month. Prescribing data from the hospital show that there have been 24 prescriptions for LDT between September 2012 and July 2013, with an average of prescriptions per patient. Making the case for LDT In establishing the LDT service, it has been important to highlight the benefits of using LDT on patients with wounds. In particular, the ability of LDT to debride wounds rapidly, minimise the need for anaesthesia and reduce antibiotic use in vulnerable patients. Although there is an initial cost outlay in using LDT, the fact that patients can be treated at home, have few complications and good outcomes, often with a single application, has meant that LDT is now no longer used as a last resort, but as a proactive choice to clean and close the wound quickly. CASE STUDIES USING LDT FROM BLACKPOOL TEACHING HOSPITALS Case study 1 Mrs M was admitted for amputation of her infected diabetic foot. Silver dressings and antibiotics were prescribed, but the wound site deteriorated and she underwent a below-knee amputation. Despite further antibiotic use and application of silver dressings, the amputation site broke down. It was decided to start LDT and discontinue antibiotic therapy. On removal of the larvae at four days, the wound bed looked healthier and a second application was applied. Mrs M was very emotional and had been reluctant to have the below-knee amputation. She was happy to receive LDT, especially as it meant that she did not have to return to theatre for further surgery. Case study 2 A 38-year-old woman with a long history of intravenous drug abuse and deep and superficial venous insufficiency, presented with infected venous leg ulcers on both legs (Figures 1 and 2). The ulcers had been present for over 10 years and were very painful, mainly due to chronic infection. The patient had a poor concordance record in the hospital and in the community. She was on methadone but was still making regular use of illegal substances. She failed to attend the leg ulcer clinic on several occasions. She had no peripheral intravenous access in both legs and arms and clinicians were reluctant to put in a central intravenous access for antibiotics and anaesthetic induction because of poor patient behaviour on more than one occasion the patient was thought to have left the ward and used the intravenous access provided by the hospital to inject drugs systemically. LDT was selected to clean her ulcers. After four days of therapy in hospital, plus leg elevation, the ulcers had improved and surgical debridement was not deemed necessary (Figures 3 and 4). The patient was discharged and treated with compression therapy in the community. Figure 1 Figure 2 Figure 3 Figure 4 Wounds UK LDT: An economic, scientific and clinical evaluation Nov (4) Suppl 18

66 EVIDENCE-BASED PRACTICE KEY POINTS A LDT service was set up to complement existing methods of debridement. Although initially a hospitalbased service, this service was extended to involve community team. Education and training were provided to support nurses using LDT. A clinical evaluation is currently in progress to look at optimising the service and assess which patients benefit most from LDT. Securing the service The LDT service in Blackpool offers an example of an integrated service where patients have good access to LDT. Referral pathways are known, and non-specialists working in the community have a good knowledge of the support networks available to them in the hospital. In a recent consensus, this was considered a key component of an ideal debridement service (see Box 1) (Wounds UK, 2013). Box 1: Components of an ideal debridement service (Wounds UK, 2013) Integrated services (primary and secondary care) so that patients/practitioners are able to access all methods of debridement where appropriate Patient information/leaflets to facilitate patient understanding of debridement and choice of techniques recommended by staff Confident practitioners who are knowledgeable about all debridement methods, decision-making and referral pathways Clear roles to ensure interventions are carried out by the most appropriate practitioner, providing the most efficient care Pathways of care with expected time frames for patients to receive treatment Clear, concise evidence-based clinical guidelines across community and acute services Rolling programme of relevant education and training with clear guidelines for non-specialists on how to access education and training Audits to measure outcomes Access to clinical photography and diagnostic services MDT support where required Increasingly, questions are raised around cost and cost-effectiveness of advanced wound care treatments (Wounds International, 2013). Within the service at Blackpool, the decision to prescribe LDT is not made solely on cost, but on safety of method (low risk) and time (eg compared to autolytic debridement, which is often seen as the low-cost first choice) (Wounds UK, 2013). However, whether an intervention provides high value depends on assessing whether its health benefits justify its costs. Plans are therefore underway for a clinical case series evaluation of LDT, led by the vascular team, to document outcomes using medical photography, clinical data collection and follow-up. This will help to quantify the potential for LDT to reduce overall costs and help confirm the benefits of using LDT in different patient groups. Encouraging the use of LDT for patients at home where possible has obvious cost savings. Working closely with the district nurses and GPs has led to a well-established service with good uptake of LDT in the community. Education on the use of LDT via the TVN advisor based at Blackpool Teaching Hospitals and training via company-based clinical nurse specialists, has been important in supporting these teams. This has led to the development of a policy document for district nurses on using larval therapy, which is being incorporated into the wound management pathway. This can be used along with existing guidelines on the use of LDT (for example: AWTVN, 2013). Removing organisational barriers to debridement The recent organisational changes within the NHS in Blackpool have brought together three different trusts, each with their own formulary. Providing consistent education and support to those working across, what is now a wider demographic area, is even more important to ensure clear rationales for prescribing. As many patients will be seen initially by practitioners working in the community, their actions and decisions about when to debride and which method to choose are key to wound progression (Wounds UK, 2013). In a recent study (Wilcox et al, 2013), researchers found that chronic wounds typically healed faster with more frequent debridement, confirming it as an integral part of caring for a patient with a wound. For optimal care, those working in acute and community care need to be supported by education to ensure they can recognise when debridement is required, know what options are open to them and receive training to ensure they have the necessary skills for debridement (Challinor, 2012). In Blackpool, improving access to resources and training has increased patient choice, with more responsive and safe care through timely referrals, ultimately helping to improve patient outcomes. REFERENCES All Wales Tissue Viability Nurse Forum (2013). All Wales Guidance for the use of Larval Debridement Therapy. AWTVN. Challinor T (2012). Uncovering the evidence on larval therapy. Wound Essentials 7 (1). Available from Wilcox J, Carter M, Covington S (2013) Frequency of debridements and time to heal. A retrospective cohort study of 312,744 wounds. JAMA Dermatol 149(9): Wounds International (2013) Making the case for cost-effective wound care. A consensus document. Wounds International. Wounds UK (2013). Effective debridement in a changing NHS: A UK consensus. Wounds UK. 19 Wounds UK LDT: An economic, scientific and clinical evaluation Nov (4) Suppl

67 EVIDENCE-BASED PRACTICE There have been many published works to support the use of larval debridement therapy (LDT) in-vitro (see pages 12 16). However, laboratory findings need to be interpreted and translated into clinical practice by clinicians using the therapy. As two tissue viability nurse specialists working in an acute hospital in Kent, we decided to evaluate the use of larvae in the debridement of haematomas based on the principles of wound bed preparation. A haematoma is frequently sustained as the result of an injury/trauma and patients often have been in hospital for several days and seen by various medical and surgical teams. In the past, LDT has been only used for these patients if other modalities were not available or when the patient was deemed unsuitable for surgical debridement. This often meant that referral to the tissue viability team for assessment and suitability of LDT was delayed; early referral would allow prompt implementation of LDT. It was therefore agreed that all patients with a haematoma would be referred to the team as soon as possible after admission, and the TVN would assess and discuss the suitability for LDT with the consultant team, providing a surgical debridement procedure was not already planned. The cases detailed below are three of the approximately 20 patients with haematoma treated with LDT over the past three years. All patients had rapid debridement compared with conventional treatments (eg hydrogels), some with one application and some with two or more treatments. After LDT, all wounds were clean and granulating, facilitating the use of conventional dressings or negative pressure wound therapy to close the wound. Rapid debridement reduced the length of stay by approximately 7 10 days. This had a beneficial effect, resulting in greater patient wellbeing and staff satisfaction. CASE 1: HAEMATOMA TO LEFT LEG Figure 3: Partial debridement was seen after four days and a second BioBag was applied. There was some excoriation of the surrounding skin due to larval secretions. This can be avoided using a skin barrier product. Figure 1: Patient with idiopathic thrombocytopaenia suffered haematoma after a fall and injury to left leg. The blood blister was incised conservatively to allow easy access for application of free-range larvae (600). There were concerns about potential bleeding and it was agreed to keep the patient in hospital for close observation during therapy. Figure 2: Larvae were removed two days later (earlier than expected) as the patient had experienced some increased pain in the leg, which was not fully relieved by analgesics. A BioBag was applied to contain the larvae and reduce discomfort/pain. Figure 4: Patient was discharged home with Hydrofiber dressings for follow-up by the district nurse. DEBORAH EVERITT Senior Tissue Viability Specialist Nurse, Darent Valley Hospital, Dartford, Kent ZOE EVANS Tissue Viability Specialist Nurse, Darent Valley Hospital, Dartford, Kent Wounds UK LDT: An economic, scientific and clinical evaluation Nov (4) Suppl 20

68 EVIDENCE-BASED PRACTICE CASE 2: HAEMATOMA TO LEFT FOREARM Figure 1: Injury to the left arm caused by a hoist sling rubbing and bruising the skin and tissues. The patient was seen by the TVN and larvae ordered. Figure 2: Hydrocolloid dressing applied to the surrounding skin to protect periwound skin and contain the free-range larvae. Figure 3: Larvae were removed three days later. Figure 4: Larvae (600) were applied for four days. After removal, wound bed comprised 100% granulation tissue. CASE 3: HAEMATOMA TO RIGHT LEG Figure 1 (left and below): The patient presented with a very swollen and tender leg. Second opinion was sought due to concern about fragility of surrounding skin and tissues and to avoid further damage during the application of larvae. Figure 2: A BioBag of larvae was applied over the haematoma. This was deemed a safer option, reducing potential complications associated with free-range larvae. Figure 3: Partial debridement was seen four days later. Due to improvement in the condition of the surrounding skin, the decision was made to apply free-range larvae. Figure 4: Good debridement was achieved following free-range application and only superficial slough remained. Patient was discharged with Hydrofiber dressings for district nurse follow-up. The patient was referred to the plastics team, but deemed unsuitable for surgery due to advanced age and comorbidities. Figure 5: The patient later presented for an unrelated problem and TVNs were able to see the fully healed area. 21 Wounds UK LDT: An economic, scientific and clinical evaluation Nov (4) Suppl

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70 EVIDENCE-BASED PRACTICE Published by Wounds UK 23 Wounds UK LDT: An economic, scientific and clinical evaluation Nov (4) Suppl

71 STANDARD OPERATING PROCEDURE DISTRIBUTION Date of Issue : 03 June 2011 Department of Pharmacy Revision Date : 01 March 2013 St John's Hospital at Howden Code : DS/3700 Livingston Written By : L McKain West Lothian Healthcare Division Approved By: Procedure to Order and Receive Medicinal Leeches Order The supplier of leeches offers a good delivery service, which allows the department to hold only a few leeches in stock. In normal circumstances leeches can be ordered and delivered within hours. Please note that these procedures apply to the working week MON to THUR only. 1. Inform the stores staff when and how many leeches are required. (Normal order quantity between leeches.) 2. Standard stores order procedures will generate an order to supplier for leeches. 3. Any need out with these days should be avoided. If Friday order means Saturday delivery then special arrangements should be made to receive the consignment. Receipt Leeches will be delivered in a plastic container within a jelly like substance. At this stage they require very careful handling. Normally the package will be delivered to the store area, which should be passed to Distribution staff 1. Ensure some Hirudo salt solution has been prepared and allowed to reach room temperature. 2. Carefully decant the leeches into a new container with hirudo salt using plastic tweezers. 3. Ensure that lid is placed on container and leeches cannot escape. 4. Count leeches and quote number received on accompanying paperwork. Pass all documents back to stores for completion of receipt process. 5. Original leech container and jelly should be placed in yellow bin for incineration Page 1 of 1

72 STANDARD OPERATING PROCEDURE DISTRIBUTION Date of Issue : 03 June 2011 Department of Pharmacy Revision Date : 01 March 2013 St John's Hospital at Howden Code : DS/3710 Livingston Written By : L McKain West Lothian Healthcare Division Approved By: Procedure to Supply Leeches to Wards Any of the wards in Burns and Plastic Surgery Unit are likely to require leeches. (Normally 4-8) The number requested depends on the size of graft and degree of congestion. The ward can normally highlight the need for leeches sometime before the real need exists and are rarely an urgent item. Prepare a label, which should follow this format :- Insert number of leeches supplied X LIVE LEECHES Ward 18 Date: KEEP SEPARATE FROM USED LEECHES Please return unused leeches to Pharmacy Standard Address Label Leeches, hirudosalt solution, leech packs and containers can be found in the big fridge on shelf no I35 1. Half fill a 150ml screw neck plastic jar with Hirudo Salt Solution and carefully transfer leeches into container. (Use tweezers and wear rubber gloves) 2. Secure lid and label as appropriate. 3. Pack the container in bubble wrapping to safely to avoid spillage during transport. 4. Leeches must be supplied to the ward with a Leech pack. See SOP Leech packs for information on how to make up a pack if none available. 5. Leeches and leech pack should then be placed in a cardboard box labelled with LIVE LEECHES HANDLE WITH CARE 6. Transport can then be arranged with porters. Page 1 of 2

73 STANDARD OPERATING PROCEDURE DISTRIBUTION Date of Issue : 03 June 2011 Department of Pharmacy Revision Date : 01 March 2013 St John's Hospital at Howden Code : DS/3710 Livingston Written By : L McKain West Lothian Healthcare Division Approved By: Leeches can attach to objects or surfaces with either end of their body. The more agitated they become the faster they become attached. If a leech cannot be removed it will probably become damaged if you persevere and try to force it off the surface. A swimming leech is easier to catch. Used Leeches should never be returned to Pharmacy they must be disposed of at ward level as per Leech information Leaflet Page 2 of 2

74 STANDARD OPERATING PROCEDURE DISTRIBUTION Date of Issue : 01 June 2011 Department of Pharmacy Revision Date : 01 March 2013 St John's Hospital at Howden Code : DS/3711 Livingston Written By : L McKain West Lothian Healthcare Division Approved By: Procedure to Make up a Leech pack Leech packs must be given to wards being supplied with Leeches Each pack contains in a clear plastic bag: 1 X 300ml Bottle of 10% Isopropyl Alcohol (Extempt worksheet no 116) 1 x 600ml Bottle of Isopropyl Alcohol 70% A copy of the Leech information leaflet Once made up the Leech pack should be placed on shelf I 35 in big fridge. Page 1 of 1

75 STANDARD OPERATING PROCEDURE DISTRIBUTION Date of Issue : 03 June 2011 Department of Pharmacy Revision Date : 03 March 2013 St John's Hospital at Howden Code : DS/3730 Livingston Written By : L McKain West Lothian Healthcare NHS Trust Approved By: Guidelines for Leech Care Temperature Ideal at 2-8 o C Store in the fridge Avoid temperature greater than 25 o C. Never sit in direct sunlight. Water Mix 0.5 grams of Hirudo Salt to 1000ml distilled water. This is ideal for leech physiology.. Aeration is unnecessary Container A lid is essential on a glass or similar vessel. Perforations or a gap are advised which must be very small since leeches can pass through extremely small openings. Maintenance of Leeches 1. Pour leeches into other vessel (ensure the receiving vessel is clean) 2. Clean the inside walls of the container with soap and water. 3. Rinse out very thoroughly with tap water 4. Put some fresh Hirudo Salt Solution (approx. 1 litre) into cleaned vessel. 5. Decant leeches into clean solution. (use same method as decanting for ward supply) 6. Transfer any stubborn leeches by first pouring off most of the dirty Solution and allowing them to settle. Then simply pour the remaining solution (with leeches) into the cleaned container - the small quantity of dirty solution should not greatly affect the animals well being. Page 1 of 1

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78 (k) Antimicrobial Dressing Definition Antimicrobial is the general name for any agent that kills or inhibits the growth or replication of bacteria. Prescribing Notes Systemic antibiotics are indicated in cases of overt wound infection where the classical signs are evident. Antimicrobial dressings are appropriate for critically colonized or locally infected wounds. Antimicrobial Dressings Ropper Ladder provides a step wise approach to managing possible infected wounds. Matrix to guide use depending on wound/tissue type Dressing For low exudate wounds For high exudate wounds Suitable for cavity wounds Aids debriding Contains honey Contains iodine Contains high dose silver Flamazine cream Medihoney Antibacterial Medical Honey Medihoney Apinate TM Medihoney Antibacterial tulle Y N Y Y N N Y Y N Y Y Y N N N Y Y Y Y N N Y N Y Y Y N N Actilite Y N Y Y Y N N Iodosorb Ointment IodoFlex Paste N Y Y Y N Y N N Y Y Y N Y N

79 ii) Honey Based Products Honey Ointment First Choice: Medihoney Antibacterial Medical Honey Absorbent Honey Dressing First Choice: Medihoney Apinate TM (alginate dressing with Manuka honey) Tulle Dressing First Choice: Medihoney Antibacterial Tulle Low Adherent Dressing First Choice: Actilite Formulations/Dose Medihoney Antibacterial Medical Honey (Medical Grade Leptospermum Honey); 20g, 50g [NPC] Medihoney Apinate TM (non-adherent calcium alginate dressing, impregnated with medical grade honey) 5cm x 5cm, 10cm x 10cm [NPC] Medihoney Antibacterial Tulle (impregnated with medical grade manuka honey) 5cm x 5cm, 10cm x 10cm [NPC] Actilite (impregnated with medical grade manuka honey and manuka oil) 10cm x 10cm, 10cm x 20cm [NPC] Prescribing Notes Honey is an antimicrobial that can also promote autolysis of necrotic or sloughy tissue. Increased exudate can be expected for up to 48 hours after first application therefore appropriate secondary dressing is required. Patients may experience a drawing sensation/pain due to the osmotic action of the honey. Actilite is suitable for low exudate wounds where antimicrobial action is required. It is more effective than Inadine as it is not affected by wound exudate. Actilite has a lower honey dose and can be used in patients who experience pain and cannot tolerate Medihoney Antibacterial Tulle. Avoid in patients with sensitivity to bee venom. Blood sugar levels should be monitored as normal in diabetic patients. Honey dressings also have deodorising properties.

80 Honey Dressing Actilite Medihoney Antibacterial Tulle Medihoney Apinate TM Medihoney Antibacterial Medical Honey When to use? Superficial wounds with minimal to no exudate that require protection, and hydration for epithelialisation to occur. Wounds with minimal-moderate exudate, that require autolytic desloughing/debridement. Wounds and cavities with moderate-high exudate, that require autolytic debridement. Wounds and cavities requiring hydration to allow autolysis/debridement to occur.

81 A step-by-step guide to aid in identifying infected wounds and using topical antimicrobial dressings Step 1 - Assessment Use the Ropper Lothian Ladder (see over) to identify the problem and guide management for infected or critically colonised wounds. Go to Step 2 Step 2 - Reducing bacterial load using surfactant products Use a cleansing solution or gel containing a surfactant to reduce bacterial load on the wound surface e.g. Prontosan solution or Prontosan Gel/Gel X (section (c) of LJF, Wound Section) Solution needs to be in contact with wound bed for minutes for full cleansing effect Gel remains on the wound until next dressing change (Gel not advised for ischaemic limbs) If gel/solution not clinically appropriate or no progress/wound deteriorating go to Step 3 Step 3 - Lothian Joint Formulary (LJF) Treatment and review If a topical antimicrobial dressing is the product of choice then refer to LJF, Adult, Wound Section, Wound Management Products, Section (k) Antimicrobial dressings for current options* Review wound no later than two weeks after commencing therapy to assess progress If unable to use LJF products of choice due to specific patient or wound issues go to step 4 Step 4 - Non-formulary options and considerations under certain clinical conditions All non-formulary antimicrobial dressings can be advised and/or prescribed by a registered practitioner who clinically manages wounds if: An infected or critically colonised wound has been treated with formulary antimicrobial dressings for up to two weeks with no progress A patient has allergies/sensitivities to the current formulary products There are specific rationale for the formulary option not being suitable for the patient/wound In these cases the following can be considered depending on exudate levels: Low exudate - These all require a secondary dressing 1. DACC dressings 2. Enzymatic 3. Silver coated sheet Reassess as Step 1, either as wound improves or after 2 weeks Moderate/High exudate - * require secondary dressing 1. DACC dressing pads 2. Enzymatic 3. PHMB 4. Silver absorbent All non-formulary dressings must be requested via pharmacy using the Non-Formulary Antimicrobial Dressings Request Form available on the intranet. Secondary care - send to pharmacy to obtain dressing and for audit purposes Primary care - prescribe dressing as normal plus complete above form and send to Patricia McIntosh, Prescribing Lead/CNM, Astley Ainslie Hospital, for audit purposes How non-formulary antimicrobials work and some examples (check BNF/Drug tariff for full listings): DACC (Dialkylcarbamoylchloride): Contains no chemical or pharmacological substance; bacteria and fungi become bound to the matrix of the dressing by a hydrophobic interaction, they cannot reproduce or release toxins once bound. Change 2-5 days E.g. Cutimed Sorbact swab or pad Enzymatic: Alginate gels which contain an enzyme complex containing glucose oxidase and lactoperoxidase, which acts as an antimicrobial. Active against bacteria, viruses and fungi. No evidence of cytotoxicity. Change 1-4 days E.g. Flaminal Hydro & Flaminal Forte PHMB (Polyhexamethylene biguanide): Disrupts bacterial cell membranes and kills bacteria by deactivating DNA. No issues with absorption into tissues and sensitization. No evidence of cytotoxicity. Change 1-7 days E.g. AMD Foam, Suprasorb X + PHMB Silver: Disrupts bacterial cell membranes and kills bacteria by deactivating DNA. May be absorbed into tissues and cause sensitization. Some evidence of cytotoxicity. Should not be used on non-infected wounds as can slow healing. Not recommended as first choice non-formulary antimicrobial. Change 1-7 days E.g. Askina Calgitrol thin, Silvercel Non-Adherent, Aquacel Ag, Acticoat & Acticoat Absorbent Before using any antimicrobial dressing always read the manufacturers guidelines, indications and contraindications Developed by TVN Team in conjunction with Public Health Consultant & LJF Pharmacist in line with NHS Lothian Policy * See for current recommendations RR-April 2013 Review date April 2015

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83 Medihoney Wound Care The Natural Choice in WOUND care What is MEDIHONEY? MEDIHONEY is a topical wound care product made with Anitbacterial Leptospermum Honey. Researchers have found that the Leptospermum species has unique plant derived components that make it ideal for the management of hard to heal wounds and burns. MEDIHONEY dressings are standardised and sterilised by gamma irradiation. The sterilisation process guarantees the removal of Clostridium botulinum spores which may be present in unsterilised honey. MEDIHONEY comes from a traceable source and is produced under hygienic conditions. It is free of pesticides and antibiotics. MEDIHONEY Anitbacterial Leptospermum Honey: Cleans the wound and rapidly lifts dead tissue. Helps to reduce oedema and wound ph. Provides a moist healing environment. History of honey use in wound care Honey has been used in wound healing for centuries. Evidence for its wide range of medicinal use has been found in ancient writings such as the Edwin Smith Papyrus in the 17th century BC. Honey was used during World War I and II but became less popular when antibiotics came into use around Only in the last decade have microbiologists begun to understand the uniqueness of the Leptospermum species. Why should I use honey on my wound? MEDIHONEY is a natural product that provides a moist wound healing environment for the wound tissue. It helps optimise wound healing without toxic side effects. There are many reasons why some wounds become chronic and do not heal. MEDIHONEY helps to counter many of these issues. Why can t I use just any honey? The honey available in stores for cooking and eating is often not sterilised and may carry a small risk of infection with bacterial spores. Additionally, only Leptospermum honey has been shown in large scale randomised controlled studies to improve wound healing versus other advanced wound care products. As compared to other medical grade honey products available, only Leptospermum honey continues to work even in the presence of catalase, an enzyme found in wound fluid and blood. Can I still use honey if I am a diabetic? Yes. You can still use MEDIHONEY. The high sugar content in MEDIHONEY has a beneficial osmotic effect, helping to cleanse the wound and remove dead tissue. Local wound care should be combined with diabetic management. Your wound should be monitored by your healthcare provider on a regular basis. Regular use of MEDIHONEY on diabetic foot ulcers has not been shown to alter glucose levels during routine monitoring. Is there a time limit for using MEDIHONEY? No. MEDIHONEY can be used from the beginning of a wound all the way to healing, making wound management much easier than with other dressings. How often should the dressing be changed? Your healthcare provider will evaluate you along with your medical history and your wound. The frequency of the dressing change will depend on your condition and the amount of drainage coming from your wound. The MEDIHONEY product can be left in place under compression and off-loading devices. However, if there is a lot of fluid and the dressing becomes saturated, it may need to be changed more frequently. Conversely, the frequency of the dressing change may be decreased if the drainage decreases. There are several formulations of MEDIHONEY for varying levels of exudate management. How do I change my dressing? Remove the dressing from the wound bed gently. If the dressing is dry and sticking to the wound bed, you may moisten it with normal saline or sterile water. When I remove the dressing why does the color of the dressing appear different? The MEDIHONEY dressing draws fluid and dead tissue away from the wound and into the dressing. The dressing may change color as a result. Also, a thin coating of honey may remain on the wound and the skin surrounding the wound. This appears as a film on the wound and is easily removed with saline or other wound cleanser. What do I do to protect my skin around the wound? As MEDIHONEY draws fluid from the wound, the dressing might become easily saturated. It is important to absorb this moisture with a cover dressing and to protect the skin around your wound with a skin protectant barrier cream. Ask your healthcare provider to suggest an absorptive cover dressing and a skin protectant barrier cream, such as Medihoney Barrier Cream, to prevent maceration from moisture. What if my wound looks larger than before? During the healing process, due to the removal of dead tissue, it is common for the wound to show an initial increase in wound size. Although an initial increase in size may be attributed to the normal removal of non-viable tissue, consult a healthcare professional if the wound continues to grow larger after the first few dressing changes.

84 Medihoney Wound Care The Natural Choice in WOUND care I have heard honey can be painful. MEDIHONEY has a low ph and helps to lower the overall ph of a wound. This provides wound healing benefits. But due to this change in ph some individuals experience a stinging sensation when MEDIHONEY is applied. If stinging occurs it usually lasts for several minutes but may last longer. If you experience any pain, your healthcare provider may suggest an analgesic which should be taken approximately 30 minutes before your dressing is changed. If the analgesic does not stop the stinging, your healthcare provider might try a different version of MEDIHONEY, such as the MEDIHONEY Antibacterial Gel Sheet dressing. If you are still uncomfortable, remove the dressing, cleanse the wound, and consult your healthcare provider. When should I not use MEDIHONEY? Do not use MEDIHONEY On third degree burns If you have a known sensitivity to alginate or honey To control heavy bleeding Is MEDIHONEY safe for use on children s wounds? Yes. MEDIHONEY is a natural product that can be used on children of all ages. MEDIHONEY is a medical grade honey and is sterilised to kill bacterial spores such as Clostridium botulinum. Managing a wound with MEDIHONEY can help a wound to heal when used along with a plan of care that is individualised for you by your healthcare provider. Derma Sciences Europe Ltd. Suites 2b & 2c 1A Park Street Maidenhead SL6 1SL U.K. Tel: +44 (0) Fax: +44 (0) THE GLOBAL LEADER IN MeDICAL-GRADE HONEY-BASED WOUND AND BURN CARE PATIENT INFORMATION GUIDE