Title Developed By. Implementation Contact person(s) Review Date Group Responsible. NICaN Policy: Management of Chemotherapy Extravasation; Version 3

Transcription

1 Title Developed By Management of Chemotherapy Extravasation NICaN Regional Pharmacy Group Version History Version 3: 2009 (See appendix 6) Version 2: January 2006 Version 1: June 2005 Consultation Period November 2008 January 2009 Endorsed By Version 1: NICaN Board, August 2005 Implementation Contact person(s) Review Date Group Responsible Version 3: NICaN Board, February 2009 Ongoing by relevant Trusts Ms Maire McGrady Chair NICaN Regional Pharmacy Group Tel: February 2012 NICaN Regional Pharmacy Group Page 1 of 19

2 NICaN Policy: Management of Chemotherapy Extravasation Table of Contents SECTION 1: General Information Purpose Summary Differential Diagnosis Symptoms of Extravasation Classification of Chemotherapy Definitions of Classifications...6 SECTION 2: Management of Chemotherapy Extravasation General Procedure for the Management of Chemotherapy Extravasation Peripheral Sites General Procedures for the Management of Mixed Extravasations Management of Extravasation from Central Venous Access Devices Definitions for Use in Conjunction with Tables 2 and Drug Specific Management Procedures...10 APPENDICES...12 Appendix 1: How to Report an Extravasation Injury to NEXIS...12 Appendix 2: Patient Information on Extravasation...13 Appendix 3: Use of Dimethylsulphoxide and Hydrocortisone 1% Cream for Treatment of a Suspected Extravasation Injury...14 Appendix 4: Hospital check list for dealing with a suspected extravasation...16 Appendix 5: References...17 Appendix 6: Version Control: Record of Changes...18 List of Tables Table 1 Classification of chemotherapy agents according to their potential to cause injury when extravasated...4 Table 2 Drug Specific Management of Chemotherapy Extravasation...11 Table 3 Definitions and additional comments for use with Table of 19

3 SECTION 1: General Information 1.1 Purpose To help practitioners who are involved in the administration of intravenous (IV) chemotherapy to recognise extravasation and successfully manage it to minimise the risk of injury. 1.2 Summary Extravasation is defined as the unintended administration of a pharmaceutical into the tissue spaces surrounding a vein during intravenous injection. The consequences are often pain, erythema, inflammation and discomfort. Damage can continue for months and involve nerves, tendons and joints. If left undiagnosed, or if treatment is delayed, surgical debridement, skin grafting, and even amputation may result. For the purposes of this policy chemotherapy means all intravenous anti-cancer treatments including cytotoxic drugs, monoclonal antibodies and biological agents. 1.3 Differential Diagnosis Incidents commonly misdiagnosed as extravasation include: 1. Discoloration reactions in the vein (some chemotherapy agents are highly coloured). 2. Venous contraction or spasm due to thermal shock. 3. Phlebitis (inflammation of the vein) due to an irritant component (e.g. etoposide) or because the ph of the formulation is particularly acidic or alkaline (e.g. doxorubicin or epirubicin). 4. Local and / or central hypersensitivity (e.g. taxanes). 5. Anaphylaxis. 1.4 Symptoms of Extravasation Burning, stinging, modest or severe pain, or any acute change at the injection site. There is a lack of blood return from the cannula. This alone is not sufficient for a definitive diagnosis of extravasation, as lack of blood return can occur without extravasation. Likewise, blood return may be possible even with an extravasation. The flow rate is reduced and possible changes in the position of the body (e.g. bending of the wrist or elbow) or cannula supports (e.g. the bandaging) have been excluded. Local blistering, mottling and darkening of the skin, induration (abnormal hardening of the tissue), erythema, venous discoloration or swelling. 3 of 19

4 If left untreated the surface of the skin may appear very white and cold with no capillary filling. A dry, black eschar may develop. Ulceration may occur as a complication of extravasation. (Ulceration is not usually evident until one or two weeks after the injury when the eschar sloughs to reveal the underlying cavity). Whilst extravasation is possible with IV injection of any chemotherapy agent it is only considered problematic with those compounds which are vesicant, exfoliant or irritant. It is the responsibility of the person administering chemotherapy to ensure that they are aware of the classification of the drug(s) before they are administered. 1.5 Classification of Chemotherapy 1 Vesicants Exfoliants Irritants Inflammatory Neutrals Agents Amsacrine Aclarubicin Arsenic Trioxide 2 Bortezomib 2 Aldesleukin (Interleukin 2) Carmustine Cisplatin Carboplatin Etoposide Alemtuzumab 2 Phosphate Chlormethine Daunorubicin Etoposide Fluorouracil Asparaginase 2 Hydrochloride (liposomal) Dacarbazine Docetaxel Irinotecan Methotrexate Bevacizumab 2 Dactinomycin Doxorubicin Teniposide Ralititrexed Bleomycin (liposomal) Daunorubicin Floxuridine Cladribine Doxorubicin Mitoxantrone Crisantaspase Epirubicin Oxaliplatin Cyclophosphamide Idarubicin Topotecan Cytarabine Mitomycin Fludarabine Paclitaxel Gemcitabine Streptozocin Ifosfamide Treosulfan α interferons Vinblastine Melphalan Vincristine Pentostatin Vindesine Rituximab 2 Vinorelbine Thiotepa Trastuzumab 2 Table 1 Classification of chemotherapy agents according to their potential to cause injury when extravasated HIGH RISK LOW RISK Table 1 is not an exhaustive list of chemotherapy agents. There are other drugs in use which have not yet been classified and for which the risk of extravasation injury is not known. Furthermore, many investigational medical products used in clinical trials are not classified in Table 1. In some instances information on the risk of extravasation injury or recommended 4 of 19

5 treatments for extravasation of investigational medical products may be available from the trial sponsor or the clinical trials pharmacist. 5 of 19

6 1.6 Definitions of Classifications Vesicants Capable of causing pain, inflammation and blistering of the local skin, underlying flesh and structures, leading to tissue death and necrosis. Exfoliants Capable of causing inflammation and shedding of skin, but less likely to cause tissue death. Irritants Capable of causing inflammation and irritation, rarely proceeding to breakdown of the tissue. Inflammatory Agents Capable of causing mild to moderate inflammation and flare in local tissue. Neutral Ostensibly inert or neutral compounds that do not cause inflammation or damage. 6 of 19

7 SECTION 2: Management of Chemotherapy Extravasation 2.1 General Procedure for the Management of Chemotherapy Extravasation Peripheral Sites 1. Stop administration of the chemotherapy (and any other infusions being administered via the affected cannula). 2. If not already being worn, put on appropriate personal protective equipment (e.g. gloves, armlets, apron, goggles). 3. Disconnect the administration device(s) but do not remove the cannula. 4. Explain to the patient that an extravasation may have occurred. 5. Seek advice from someone who has experience in the administration and handling of chemotherapy and assessing extravasation, according to local arrangements. 6. Report the incident to medical staff immediately. 7. Mark the area affected by extravasation with a pen. Record the size (diameter, length and width) of extravasated area in the patient s notes for future comparison. 8. Attach a 20mL syringe and attempt to withdraw residual drug. Try to draw some blood back from the cannula. 9. Consult table 2 for any drug specific treatment and follow the instructions provided in table 3. Then return to point 10. If there is no specific treatment recommended in table 2 then proceed directly to point 10. If the causative drug is an unlicensed clinical trial drug contact the clinical trials pharmacist for further advice. Out of hours contact the investigator for the clinical trial. 10. Remove the cannula. 11. If no specific management is recommended in table 2 apply 1% hydrocortisone cream to the affected area. Avoid applying pressure (pressure will increase the area of extravasation). 12. Provide analgesia if required. 13. Document the incident in the patient s medical / nursing notes and complete a Trust Incident Report form. 14. Complete an Extravasation Report and send to The National Extravasation Information Service (NEXIS) (see appendix 1). 15. Elevate the limb for 48 hours. 16. Ask the patient to observe the site and report any changes or deterioration. 17. Photographing the area within 24 hours would be desirable. Follow up photographs should be taken at one week, one month and pre and post surgery if required. 18. Any extravasation involving vesicant, exfoliant or irritant drugs should be reviewed after 24 hours and at appropriate intervals until resolution. 19. Provide appropriate written information to the patient (see appendices 2 and 3). 7 of 19

8 20. If a vesicant extravasation injury has occurred the patient s management must be discussed with a member of the medical team. The medical team will decide if admission to an appropriate ward is required. (It may be useful to use the checklist in appendix 4 to ensure that all necessary actions have been completed). 2.2 General Procedures for the Management of Mixed Extravasations 2 In the event of a mixed extravasation of agents from different classifications the following applies: The order of precedence of treatment for the different classification is vesicants > exfoliants > irritants > inflammatory agents > neutrals. Vesicant management takes precedence over exfoliants, irritants or inflammatory agents. For mixed extravasations from drugs in different classifications, apply the temperature compression of the drug that takes precedence. For drugs of the same classification, those requiring cold compression take precedence over applying hot compression apply cold compression. 2.3 Management of Extravasation from Central Venous Access Devices The incidence of extravasation using central catheters is lower, but the severity of the injuries that occur may be far greater. This is due to later detection and greater volumes of a drug with vesicant or exfoliant potential being infused. Damage may occur in the superficial tunnel section, or in the deep tissues. If a patient complains of changes in sensation, pain, burning, or swelling at any point along the pathway of the catheter or in the ipsilateral chest, or if a change in IV flow rate occurs, then extravasation may have occurred. Extravasation in the tunnelled subcutaneous section is treated in the same way as other cytotoxic extravasation injuries (see section 2.1). A diagnosis of extravasation in the tunnelled subcutaneous section is most readily made if 10mL of sodium chloride 0.9% is injected rapidly down the line. This will usually raise a bleb at the point of damage or leakage from the line, thus allowing targeting of further treatment. Extravasation in the deep implanted area is rare but far more serious. If suspected, the patient requires admission for analgesia, parenteral antibiotics and assessment. Local debridement may be necessary and plastic surgeons may need to be involved for reconstruction if skin necrosis or necrotising fasciitis have occurred. 8 of 19

9 2.4 Definitions for Use in Conjunction with Tables 2 and 3 Warm Compression, Warm Continuous Compression, W.C.C. 3 This involves applying firmly, but without undue pressure, a heat source (covered hot water bottle, small electrically heated blanket or hot pack) to the area continuously for 24 hours. The heat source should not be placed directly on the skin. A non adherent dressing should be laid in between. This assists the natural dispersal of the drug. Cold Compression, Pulsed Cold Compress, P.C.C. 3 This involves applying firmly, but without pressure, a cold source (crushed ice, flexible cold pack or cold bandage) intermittently (for 30 minutes in every 2 hours) over the area for the first 24 hours, unless advised otherwise. The cold source should not be placed directly on the skin. A non adherent dressing should be laid in between. Pin-Cushion Technique 1 The pin-cushion technique involves instilling small volumes ( mL) of fluid or antidote around and over the area affected by the extravasation. This is done by marking and measuring the circumference of the injury, and then starting at 12 o clock and injecting every two hours on an imaginary clock face (i.e. 2 o clock, 4 o clock etc). The injections are administered using a blue (23 gauge x 1inch), or orange (25 gauge x 5/8inch) needle, and towards the centre of the clock-face. For large extravasation of greater diameter than 2cm, further injections are made down imaginary radial arms, always moving towards a final injection at the centre of the clock-face. The total volume of fluid, hyaluronidase or antidote is thus determined by the size or spread of the injury. However, it is rare for more than 5mL to be required. Spread & Dilute This is a treatment strategy that promotes dispersal of any residual drug to lower its concentration in the tissues, thereby minimising any injury. This typically involves administration of hyaluronidase and use of warm compression. Localise & Neutralise This is a treatment strategy that reduces the dispersal of any residual drug and aims to render it less harmful. This typically involves administration of an antidote and use of cold compression. 9 of 19

10 2.5 Drug Specific Management Procedures DRUG Spread & Dilute Localise & Neutralise Management (Refer to Table 3) Aclarubicin No Yes A Aldesleukin (Interleukin 2) Yes No B Amsacrine No Yes A Arsenic Trioxide Yes No General 3 Bleomycin Yes No B Carboplatin Yes-after 1 st 24hrs Yes-during initial C 3 inflammatory reaction Carmustine No Yes D Chlormethine Hydrochloride No Yes E Cisplatin Yes-for treatment administered within 24hrs Yes-for treatment commenced 24hrs post extravasation F (see additional comments) Cladribine Yes No B Crisantaspase Yes No B Cyclophosphamide Yes No B Cytarabine Yes No B Darcarbazine No Yes A Dactinomycin No Yes A Daunorubicin No Yes A Liposomal Daunorubicin No Yes G 5 then A (see additional comments) Docetaxel Yes No H Doxorubicin No Yes A 1 Liposomal Doxorubicin No Yes G 5 then A (see additional comments) Epirubicin No Yes A 1 Etoposide Yes No G 3 Etoposide Phosphate Yes No G 3 Fludarabine Yes No B Fluorouracil No Yes G 3 Gemcitabine Yes No B Idarubicin No Yes A 1 Ifosfamide Yes No B α-interferon Yes No B Irinotecan Yes No G 4 Melphalan Yes No B Methotrexate No Yes G 3,4 Mitomycin No Yes A Mitoxantrone No Yes C 2 Oxaliplatin Yes No I Paclitaxel Yes No H (see additional comments) Pentostatin Yes No B Streptozocin No Yes A Teniposide No Yes G 4 Thiotepa Yes No B Topotecan No Yes D Vinblastine Yes No J Vincristine Yes No J Videsine Yes No J Vinorelbine Yes No J 1 Consider early referral to a plastic surgeon, as local debridement/reconstruction may be required. 2 Apply hydrocortisone 1% cream in an alternating regime with dimethylsulphoxide as per appendix 3. 3 When the local reaction has subsided, the use of warm compression can aid dispersal of any residual fluid. 4 Further treatment of the patient should be symptomatic. 5 Use pulsed cold compression for up to 12 hours. 10 of 19

11 Table 2 Drug Specific Management of Chemotherapy Extravasation A Apply topical dimethylsulphoxide at the extravasation site. Once the area has dried, apply hydrocortisone 1% cream followed by 30 minutes cold compression. Repeat every 2 hours for the first 24 hours after extravasation. For the next 7 to 10 days, apply dimethylsulphoxide every 6 hours alternating with hydrocortisone 1% cream, so that treatment is being applied every 3 hours on an alternating basis. Avoid contact with good skin. If blistering occurs, stop applying dimethylsulphoxide and seek further advice B If a large volume has extravasated aspirate as much fluid as possible. Where a large volume is present in tissues, causing the patient pain, use the pin cushion technique to infiltrate the site with hyaluronidase (1500units in 2mL water for injection or sodium chloride 0.9%). Apply heat and compression to assist natural dispersal of the drug. C Aspirate as much fluid as possible. Give 100mg hydrocortisone injection via the cannula. Administer 100mg hydrocortisone by subcutaneous injection, in 0.2mL aliquots, around the circumference of the affected area. Apply hydrocortisone 1% cream and cover the affected area with an ice pack, on an intermittent basis, for the first 24 hours. D Follow general procedure of management of cytotoxic extravasation (section 2.1). At point 11 treat with cold compression. E Using the pin cushion technique infiltrate the area with 1 to 3mL sodium thiosulphate 2.98% followed by 100mg hydrocortisone injection to the infiltrated area. Apply cold compression intermittently for 12 hours. F Using the pin cushion technique infiltrate the affected area with 1 to 3mL of sodium thiosulphate 2.98%. Aspirate back, then give 1500units of hyaluronidase around the area. Apply heat and compression. G Give 100mg hydrocortisone injection via the cannula. Administer 100mg hydrocortisone by subcutaneous injection, in 0.2mL aliquots, around the circumference of the affected area. Apply hydrocortisone 1% cream and treat with pulsed cold compression for up to 24 hours. H Reconstitute 100mg hydrocortisone injection and mix with 10mg chlorphenamine injection, in a volume of 10mL. Infiltrate the extravasated area with 1 to 3mL of this mixture as 0.2mL pin cushion subcutaneous injections. Depending on the size of the area it may not be necessary to use the whole 3mL. Large volume extravasations may need as much as 10mL. Follow this with 1500units of hyaluronidase and warm compression. Use topical antihistamine cream for 4 days. In particularly severe cases give 1g sodium cromoglycate orally as soon as possible after injury. This can be followed by oral sodium cromoglycate 200mg four times daily for the next 3 days. I Infiltrate the area with hyaluronidase (1500units in 2mL water for injection) using the pin cushion technique. Gently massage the area to facilitate dispersion. Treat with warm compression. Depending on the nature and severity of the extravasation the medical team should consider the following: prescribe high dose oral steroids (dexamethasone 8mg twice daily for 2 to 3 days), prescribe oral analgesia (e.g. diclofenac SR 75mg twice daily) and consider a gastroprotective agent. Consider referring the patient to Plastic Surgeon and/or Physiotherapy. J Infiltrate the area with hyaluronidase (1500units in 2mL water for injection or sodium chloride 0.9%), in 0.2mL aliquots, over and around the circumference of the affected area. Treat the affected area with warm compression for the first 24 hours. For the next 7 days apply a nonsteroidal anti-inflammatory cream to the affected area, four times daily. Cisplatin Liposomal Daunorubicin & Liposomal Doxorubicin Paclitaxel As an intact molecule, cisplatin causes few problems when extravasated. Problems arise when it is left untreated. Within 4 to 6 weeks of an acute event a subcutaneous deposit of platinum precipitates in the tissues causing pain, inflammation and necrosis. Injuries not treated within 24 hours should be treated with intermittent cold compression and managed symptomatically. Whilst the drug contained within the liposome is a vesicant, the formulation offers some protection. If untreated, liposomes may be degraded in the body over the next 2-3 weeks resulting in a full-blown extravasation within the next 7 to 10 days. Inflammation and soft tissue reactions at the injection site have been reported after infusion of paclitaxel. This can progress to serious necrotic injury if not treated promptly. Paclitaxel has a greater risk classification than docetaxel because of the cremophor in its formulation. Prolonged infusions should be avoided. Table 3 Definitions and additional comments for use with Table 2 11 of 19

12 APPENDICES Appendix 1: How to Report an Extravasation Injury to NEXIS NEXIS collates and analyses data on the treatment and treatment outcomes arising from extravasation incidents. It is hoped that this data will enable identification of the most effective treatments for extravasation and provide an evidence base for their use. In addition to documenting the incident (in the patient s medical/nursing notes and on an incident report), all extravasation incidents involving chemotherapy must be reported to NEXIS. There are two ways to report an extravasation (i) by post and (ii) online. The information required in each method is identical. Online reporting is recommended. Procedure for reporting by post Obtain an extravasation report card ( Green Card ). The extravasation report cards are available from hospital pharmacy departments. Complete the larger top section of the card and separate it from the smaller bottom section at the perforations. Make a photocopy of the completed top section and file the copy in the patient s medical notes. Fold and seal the top section for posting as shown. Post the report card to NEXIS. It is pre-printed with the address and postage is prepaid. Retain the smaller bottom section of the card in the patient s medical notes for follow up reporting. On review or resolution of the injury complete the retained follow up section. Make a copy for filing in the patient s medical notes and mail the original to NEXIS. Procedure for online reporting Access the NEXIS website at and follow the link to REPORT A NEW EXTRAVASATION INCIDENT. Complete the information asked for on the online report form. Print a copy of the completed form and file in the patient s medical notes. Click on the SUBMIT button at the bottom of the form to transmit it to NEXIS. On review or resolution of the injury access the NEXIS website at and follow the link to FOLLOW-UP REPORT OF A PREVIOUSLY REPORTED EXTRAVASATION. Complete the follow-up report (you will require the reference number from the original report previously filed in the medical notes). Print a copy to be filed in the patient s medical notes. Click on the SEND FOLLOW-UP REPORT button at the bottom of the form to transmit it to NEXIS. 12 of 19

13 Appendix 2: Patient Information on Extravasation You have been given this information sheet because it is suspected that you may have had an extravasation during administration of your chemotherapy. What is extravasation? Extravasation is the accidental leakage of a drug into the tissue surrounding a vein during intravenous administration. Extravasation is a rare occurrence and can be difficult to diagnose as the signs are similar to other problems that may occur with the administration of intravenous drugs. Extravasation can be a serious problem if it is not treated properly. However, when recognised early most extravasations can be dealt with easily and do not result in any lasting problems. What treatment is required? The initial treatment for your suspected extravasation will have been completed in the hospital. In some cases no further treatment is required. However, occasionally it may be necessary to use additional treatment for a few days afterwards. If you need to use any additional treatment you will be provided with the necessary medicines and given information on how to use them properly. What else do I need to do? In addition to using any recommended treatments you should keep the affected limb elevated for the first 48 hours. This may be done by simply using some pillows to support it in a raised position. It may be necessary for the hospital to check how things are following day. In many cases this can be done by contacting you by telephone. However, in some cases it may be necessary for you to attend the hospital so that the affected area can be examined. You will be told what arrangements have been made for you. It is also important to note that the leakage of some drugs may show no immediate signs but may develop over the following 7 to 10 days. If this should occur contact the Haematology / Oncology telephone helpline. At any stage, if you are concerned that your extravasation is not healing or is getting worse you should contact the Haematology / Oncology telephone helpline. Does extravasation affect any future treatment that I need? Extravasation should not stop you from completing your planned course of treatment. However, if you are returning to have further treatment (including more chemotherapy or radiotherapy), please tell the staff looking after you that you have previously been treated for a suspected extravasation. 13 of 19

14 Appendix 3: Use of Dimethylsulphoxide and Hydrocortisone 1% Cream for Treatment of a Suspected Extravasation Injury Extravasation occurs when a drug leaks out of the vein. You are being treated for a suspected extravasation injury. This treatment will help to prevent or lessen any further problems. You will need to apply a liquid (dimethylsulphoxide) and a cream (hydrocortisone 1%) to the affected area for a further 7 to 10 days. Apply dimethylsulphoxide every six hours alternating with hydrocortisone cream, so that the treatment is being applied every three hours on an alternating basis. It is not necessary to wake during the night to apply the dimethylsulphoxide liquid or 1% hydrocortisone cream. You will be told if you need to attend the hospital during this time. How is dimethylsulphoxide liquid applied? 1. After washing your hands, put on a pair of disposable gloves. 2. Moisten a cotton wool ball with dimethylsulphoxide. 3. Dab the skin inside the affected area with the dimethylsulphoxide moistened cotton wool, avoid contact with good skin. 4. You may experience some stinging on application of dimethylsulphoxide. 5. Ensure dimethylsulphoxide is allowed to air dry on the marked area. 6. Apply dimethylsulphoxide liquid every six hours as directed. 7. Patients treated with dimethylsulphoxide may notice a garlic like taste and odour on their breath. This is quite normal. 8. If dimethylsulphoxide is splashed into the eyes, wash immediately with cold water. Seek medical advice if pain or discomfort is experienced. 9. If blistering of the skin occurs stop using dimethylsulphoxide and contact the hospital for advice. How do I apply hydrocortisone 1% cream? 1. Wash your hands before and after applying hydrocortisone 1% cream. 2. Apply sufficient cream to thinly cover the affected area. Store all medicines out of the reach and sight of children HOSPITAL CONTACT NUMBER 14 of 19

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16 Appendix 4: Hospital check list for dealing with a suspected extravasation Initial treatment administered Patient provided with information (appendices 2 and/or 3) Patient provided with take home treatments (as appropriate) Dimethylsulphoxide Hydrocortisone Cream Hot / cold pack Analgesia Review arranged (for ALL vesicants, exfoliants and irritants): Telephone Return to hospital Documentation completed: Medical notes Nursing notes Incident report Green Card completed and sent to NEXIS (see appendix 1) Follow-up completed: 24 Hour review Long term review Green Card follow-up completed (see appendix 1) 16 of 19

17 Appendix 5: References 1. Allwood, Stanley & Wright (Eds) The Cytotoxic Handbook (4 th Edition) 2002, Radcliffe Medical Press. 2. NHS Tayside Extravasation Policy for All Drugs, Chemotherapy and Non- Chemotherapy (accessed online at on January 22, 2009) 3. West Midlands Regional Chemotherapy Services Extravasation Treatment Protocol 2005 (accessed online at on January 22, 2009) 17 of 19

18 Appendix 6: Version Control: Record of Changes The following amendments have been made in Version 3: Version 2 Section Title Description or comment of changes made to produce version 3 Changed to Management of Chemotherapy Extravasation Purpose Inserted section 1.1 Changed to: To help practitioners who are involved in the administration of intravenous (IV) chemotherapy to recognise extravasation and successfully manage it to minimise the risk of injury. Section 1.1 Changed to section 1.2 Inserted: For the purposes of this policy chemotherapy means all intravenous anti-cancer treatments including cytotoxic drugs, monoclonal antibodies and biological agents. Section 1.2 Changed to section 1.3 Point 1 cytotoxic changed to chemotherapy agents Section 1.3 Changed to section 1.4 Reworded to: Whilst extravasation is possible with IV injection of any chemotherapy agent it is only considered problematic with those compounds which are vesicant, exfoliant or irritant. It is the responsibility of the person administering chemotherapy to ensure that they are aware of the classification of the drug(s) before they are administered. Section 1.4 Changed to section 1.5 Change title to Classification of Chemotherapy Reference 1 inserted Inserted arsenic trioxide, asparaginase, bevacizumab, Table title changed to Table 4 Classification of chemotherapy according to their potential to cause injury when extravasated Inserted Table 1 is not an exhaustive list of chemotherapy agents. There are other drugs in use which have not yet been classified and for which the risk of extravasation injury is not known. Furthermore, many investigational medical products used in clinical trials are not classified in Table 1. In some instances information on the risk of extravasation injury or recommended treatments for extravasation of investigational medical products may be available from the trial sponsor or the clinical trials pharmacist. Definitions of groups changed to section 1.6 entitled Definitions of Classifications Section 2 Title changed to Management of Chemotherapy Extravasation 18 of 19

19 Version 2 Section Description or comment of changes made to produce version 3 Section 2.1 Section 2.2 Title changed to General Procedure for the Management of Chemotherapy Extravasation Peripheral Sites. Points 1 to 17 changed wording and order. Additional points added. Reference 2 inserted. First bullet point: neutrals added. Order of bullet points changed Section 2.3 Changed definitions for use in conjunction with table 2.1 to section 2.4.Definitions for use in Conjunction with Tables 2 & 3. Changed reference number 4 to reference number 3. Changed reference number 5 to 1. Spread and dilute included in definitions. Localise and neutralise included in definitions. Order of definitions changed. Removed definition of hypodermoclysis. Under definition for pin cushion marked has been changed to affected ml and mls changed to ml. Section 2.4 Changed to Section 2.5 Table title changed to Drug Specific Management Procedures New drugs added arsenic trioxide. Table reformatted. References for oxaliplatin removed Section 3.1 Section 3.2 Appendices Appendix 1 Patient information on extravasation removed as this policy does not cover prevention Changed to appendix 3. Title changed to Use of Dimethylsulphoxide and Hydrocortisone 1% Cream for Treatment of a Suspected Extravasation Injury. DMSO removed. Changed wording of how to apply Dimethylsulphoxide at points 2 and 7. Inserted keep out of reach and sight of children. Inserted appendix 1 How to Report an Extravasation Injury to NEXIS Inserted appendix 2 Patient Information on Extravasation Inserted appendix 4 Hospital check list for dealing with a suspected extravasation Changed to appendix 5. Some references removed 19 of 19