Protocol for Management of Chemotherapy Extravasations

Chemotherapy Executive Group at St Chad’s Unit, City Hospital Birmingham, UK

Treatment of Extravasation
Purpose
To help practitioners prevent, recognise and successfully treat extravasation injuries from chemotherapy.
Prevention
The position, size and age of the venepuncture site are the factors, which have greatest bearing on the likelihood of problems occurring. However, if the following points are borne in mind, the likelihood of extravasation can be significantly reduced.For slow infusion of high-risk drugs, a central line or PIC line should be usedTo ensure patency of a peripheral IV site, it is best to administer cytotoxics through a recently sited cannula. Site the cannula so it cannot become dislodged; use the forearm and avoid, if possible, sites near joints.Administer vesicants by slow IV push into the side-arm port of a fast-running IV infusion of compatible solution.The most vesicant drug should be administered first.Assess a peripheral site continually for signs of redness or swelling.Verify patency of the IV site prior to vesicant infusion and regularly throughout; if there are any doubts, stop and investigate. Resite the cannula if the patency of the cannulation is still not entirely satisfactory.Ask the patient to report any sensations of burning or pain in the infusion site. Some investigators suggest delaying the administration of antiemetics until after vesicant administration. The sedative and anti-inflammatory effects of antiemetics often mask the early warning signs of extravasation and may impede the patient’s ability to report any sensation at the infusion site.Never hurry. Administer drugs slowly to allow the drug to be diluted by the carrier solution and to allow careful assessment of the IV site.Document carefully the rate of administration, location and condition of site, verification of patency, and patient’s responses, on giving any potentially extravasable drugs.If vein diameter or vein collapse are a problem, then the use of glyceryl trinitrate patches distal to the cannula may be helpful.

Recognition
Extravasation should be suspected when:The patient complains of burning, stinging, pain or any acute change at the injection site. The patient is often the first person to become aware that something is wrong with their IV therapy, so instruct them at the beginning of treatment to inform staff of any acute change during treatment. Explain the reason for this in a way, which is not frightening but conveys the need for the patient’s input and participation. Give reassurance that, if a leakage of drug should occur, it would probably not cause serious problems if the infusion is promptly stopped and the correct treatment instituted. Patients who are unable to communicate should be closely observedInduration, erythema, venous discoloration or swelling is observed at the site (discoloration alone may not indicate extravasation as doxorubicin, epirubicin and mitozantrone have been reported to produce this)No blood return is obtained. A lack of blood return from the cannula is commonly quoted as a sign that extravasation has occurred. It is however, the most misleading of all signs and has been implicated in a number of serious incidences. This occurs because although there has been extravasation injury and the cannula has become displaced, the act of trying to draw blood back to test for blood return moves the cannula back into the vein. Thus blood is returned, however, there is a hole in the vein wall in the proximity of the cannula tip. So when administration recommences, a larger and more significant extravasation injury ensues. Alternatively, the bevel of the needle can puncture the vein wall during venepuncture, allowing drug to escape into the tissue whilst the lumen of the needle may still remain in the blood vessel and allow adequate blood return.The flow rate is reduced. A reduced rate may be observed when using an infusion pump, so close observation is necessary.Increased resistance to the administration, once possible changes in the position of the body e.g. bending of wrist or elbow, or cannula support e.g. the bandaging, have been excluded as possible causes of the increased resistance, then a displaced cannula and hence extravasation are the next most likely causes. This is often one of the first signs of a problem or of pre-extravasation syndrome.Once the alternative diagnoses have been considered and excluded and one or more of these symptoms are present, the practitioner should proceed on the basis of a diagnosis of extravasation.

Basic Treatment

ALWAYS: Aspirate extravasation injuries and inject steroid hydrocortiscone subcutaneously to the affected area and IV if large-scale inflammation, flare or fracturing along the vein has occurred.Treatment is then characterised as:
EITHER ‘Spread and Dilute’ using: Normal salineHyaluronidaseWarm, continuous compression and elevation of limb 
OR ‘Localise and Neutralise’ using: Antidote if availableIntermittent cold compression
MOST IMPORTANTLY It is vital to act promptly.Act in a manner that will not aggravate the injury but a manner that offers prompt first aid treatment.
General procedure for the management of extravasation
Seek experienced assistance from someone used to looking at extravasation.Stop infusion, disconnect the drip but….
DO NOT REMOVE THE VENFLON. Mark the extravasated area with a pen.Aspirate the extravasated drug, trying also to draw some blood back from the cannula/venflon. This may be facilitated by s.c. injection of either 0.9% sodium chloride, to dilute the drug, or 1500 units of hyaluronidase in 2ml water for injection, to ‘open’ up the intracellular space.Remove the venflon.
Give hydrocortisone (2ml) as 0.1-0.2ml sc injections at about 6 to 8 points around the circumference from the extravasation site.
Give 100mg hydrocortisone IV if large-scale inflammation, flare or fracturing along the vein has occurred. This should be administered via a new venflon, resited remotely from the extravasation area.Consult the individual management chart for specific treatments, and/or the National Extravasation Information Service on 0121-554-3801 bleep
3007 or www.extravasation.org.uk
Instruct the patient on the correct care of the site and on the use of any ongoing treatment. Analgesics may be required for pain management.Complete the green card extravasation report card
Ensure that the extravasation is followed up. Counsel the patient that if the symptoms worsen in the following days then they should promptly contact their clinic or ward. 

Classification
Classification of cytotoxic drugs according to their potential to cause serious necrosis when extravasatedPlease note that the groupings have been reversed as of October 2005 – this is in order to facilitate the formulation of a grading system for extravasation risk – the higher the grouping, the higher the risk of causing severe and serious tissue damage. For any queries, please contact Andrew Stanley. 

Neutrals:Group 1Inflammitants:Group 2Irritants:Group 3Exfoliants:Group 4Vesicants:Group 5
AsparaginaseEtoposide PhosphateCarboplatinAclarubicinAmsacrine
BleomycinFluorouracilEtoposideCisplatinCarmustine
CladribineMethotrexateIrinotecanDaunorubicin LiposomalDacarbazine
CyclophosphamideRaltitrexedTeniposideDocetaxelDactinomycin
Cytarabine  Doxorubicin LiposomalDaunorubucin
Edroclomab  FloxuridineDoxorubicin
Fludarabine  MitozantroneEpirubicin
Gemcitabine  OxaliplatinIdarubicin
Ifosfamide  TopotecanMitomycin
Melphalan   Mustine
Pentostatin   Paclitaxel
Rituximab   Streptozocin
Thiotepa   Treosulfan
Beta-Interferons   Vinblastine
Aldesleukin (IL-2)   Vincristine
Trastuzemab   Vindesine
    Vinorelbine

Individual Drug Management

nb. Group numbering has been changed as of October 2005 – see above for info.

DRUGGROUPASPIRATEAnd instillsteroids001‘SPREAD’ AND DILUTELOCALISE AND NEUTRALISESPECIFIC MANAGEMENTADDITIONALINFORMATION
Aclarubicin4YYApply topical DMSO, every 2 hours at the extravasation site followed by topical hydrocortisone cream and a cold compress.1 hAvoid contact with good skin. If blistering occurs, stop the DMSO and seek further advice
Aldesleukin (IL-2)1YYInfiltrate the site with hyaluronidase Apply heat and compression.2 g 
Amsacrine5YYApply topical DMSO, every 2 hours at the extravasation site followed by topical hydrocortisone cream and a cold compress.1 hAvoid contact with good skin. If blistering occurs, stop the DMSO and seek further advice
Asparaginase1YYInfiltrate the site with hyaluronidase Apply heat and compression.2 gRe-test for asparaginase hypersensitivity before giving further doses
Bleomycin1YYInfiltrate the site with hyaluronidase.Apply heat and compression.2 g 
Carboplatin3YYiYiInfiltrate the site with hyaluronidase.Followed by topical hydrocortisone and warm compression. 2 gPossibility of local inflammation or necrosis and/or pain. There are no specific antidotes. Although 3% thiosulphate may be useful
Carmustine 5YYInfiltrate with 2.1% sodium bicarbonate,c leave for two minutes and aspirate off again.Sodium bicarbonate is a Vesicant. Topical contact with carmustine may induce hyperpigmentation
Cisplatin4YYiYiInfiltrate the site with 3% thiosulphate,b aspirate back, then give hyualuronidase.Followed by topical hydrocortisone and warm compression.2 g 
Cladribine1YYInfiltrate the site with hyaluronidase.Apply heat and compression.2 g 
Cyclophosphamide1YYInfiltrate the site with hyaluronidase.Apply heat and compression.2 g 
Cytarabine1YYInfiltrate the site with hyaluronidase.aApply heat and compression.2 g 
Dacarbazine5YYApply topical DMSO, every 2 hours at the extravasation site followed by topical hydrocortisone cream and a cold compress.1 hAvoid contact with good skin. If blistering occurs, stop the DMSO and seek further advice. Patients should avoid intense exposure of the effected area to sun light after extravasation. Surgical excision e is sometimes required to prevent serious damage
Dactinomycin5YYApply topical DMSO, every 2 hours at the extravasation site followed by topical hydrocortisone cream and a cold compress.1 hAvoid contact with good skin. If blistering occurs, stop the DMSO and seek further advice. Surgical excision e is sometimes required to prevent serious damage
Daunorubicin5YYApply topical DMSO, every 2 hours at the extravasation site followed by topical hydrocortisone cream and a cold compress.1 hAvoid contact with good skin. If blistering occurs, stop the DMSO and seek further advice. Surgical excision e is sometimes required to prevent serious damage
Daunorubicin Liposomal4YYApply topical hydrocortisone and cover the area with an ice pack for up to 12 hours, h then at 8-12 hours post incidence apply DMSO 2 hourly for the next 24 hours.3Avoid contact with good skin. If blistering occurs, stop the DMSO and seek further advice
Docetaxel4YYInfiltrate the area with a mixture d of hydrocortisone and chlorpheniramine as 0.2ml ‘pin cushion’ subcutaneous injections. Follow by hyaluronidase and then warm compressions g alternated with the application of topical antihistamine cream.4 In severe cases 1g of oral sodium cromoglycate should be administered as soon as possible after the injury. 
Doxorubicin5YYApply topical DMSO, every 2 hours at the extravasation site followed by topical hydrocortisone cream and a cold compress.1 hAvoid contact with good skin. If blistering occurs, stop the DMSO and seek further advice. Sodium bicarbonate may have a roleSurgical excision e is sometimes required to prevent serious damage
Doxorubicin Liposomal4YYApply topical hydrocortisone and cover the area with an ice pack for up to 12 hours, h then at 8-12 hours post incidence apply DMSO 2 hourly for the next 24 hours.3Avoid contact with good skin. If blistering occurs, stop the DMSO and seek further advice
Epirubicin     5YYApply topical DMSO, every 2 hours at the extravasation site followed by topical hydrocortisone and a cold compress.1 h Avoid contact with good skin. If blistering occurs, stop the DMSO and seek further advice. Sodium bicarbonate may have a role. Surgical excision e is sometimes required to prevent serious damage
Etoposide3YYApply topical hydrocortisone and cover the area with an ice pack. 2 hPossibility of local inflammation or necrosis and/or pain . There are no specific antidotes.
Etoposide Phosphate2YYApply topical hydrocortisone and cover the area with an ice pack h for the next 4 hours. If the local reaction has then settled apply heat g for a further 24 to 48 hours. 2Possibility of local inflammation. S/C hyaluronidase may facilitate dispersion of large volume extravasations in addition to the warm compressions
Floxuridine4YYInfiltrate with sodium bicarbonate c into the area, followed by heat (i.e. warm compress g)Extravasation is rare.See j
Fludarabine1YYInfiltrate the site with hyaluronidase.Apply heat and compression.2 g 
Fluorouracil2YYApply topical hydrocortisone and cover the area with an ice pack h for the next 4 hours. If the local reaction has then settled apply heat g for a further 24 to 48 hours. 2Possibility of local inflammation. S/C hyaluronidase may facilitate dispersion of large volume extravasations in addition to the warm compressions
Gemcitabine1YYInfiltrate the site with hyaluronidase.Apply heat and compression.2 g 
Idarubicin5YYApply topical DMSO, every 2 hours at the extravasation site followed by topical hydrocortisone cream and a cold compress. 1 hAvoid contact with good skin. If blistering occurs, stop the DMSO and seek further advice. Sodium bicarbonate may have a role. Surgical excision e is sometimes required to prevent serious damage
Ifosfamide1YYInfiltrate the site with hyaluronidase.Apply heat and compression.2 gUnlikely to cause tissue damage
Irinotecan3YYInfiltrate with sodium bicarbonate into the area, followed by heat (i.e. warm compression.g)Extravasation is rareSee j
Beta Interferons1YYInfiltrate the site with hyaluronidase.Apply heat and compression. 2 g 
Melphalan1YYInfiltrate the site with hyaluronidase.a Apply heat and compression. 2 g 
Methotrexate2YYApply topical hydrocortisone and cover the area with an ice pack h for the next 4 hours.If the local reaction has then settled apply heat g for a further 24 to 48 hours. 2Possibility of local inflammation. S/C hyaluronidase may facilitate dispersion of large volume extravasations in addition to the warm compressions
Mitomycin5YYApply topical DMSO, every 2 hours at the extravasation site followed by topical hydrocortisone cream and a cold compress. 1 hAvoid contact with good skin. If blistering occurs, stop the DMSO and seek further advice. Surgical excision e is sometimes required to prevent serious damage
Mitozantrone4YYApply topical DMSO, every 2 hours at the extravasation site followed by topical hydrocortisone cream and a cold compress. 1 hPossibility of local inflammation or necrosis and/or pain
Mustine5YYInfiltrate the area with sodium thiosulphate.Introduce a further 100 mg of hydrocortisone to the infiltrated area. Apply cold compression for 12 hours.hSurgical excision e is sometimes required to prevent serious damage
Oxaliplatin4YYInfiltrate with hyaluronidase and a 500 ml bag of 5% dextrose plus further hyaluronidase a should be placed in the centre of the extravasation area in a ‘hypodermoclysis’ f fashion, the area warmed to aid dispersion. The fluid should be left up to 8 hours or until the 500ml is dissipated.Caution in diabetic patients
Paclitaxel5YYInfiltrate the area with a mixture d of hydrocortisone and chlorpheniramine as 0.2ml ‘pin cushion’ subcutaneous injections. Follow by hyaluronidase and then warm compressions g alternated with the application of topical antihistamine cream.4 In severe cases 1g of oral sodium cromoglycate should be administered as soon as possible after the injury and can be followed by 200mg four times a day for the next three days 
Pentostatin1YYInfiltrate the site with hyaluronidase.Apply heat and compression.2 g 
Raltitrexed2YYApply topical hydrocortisone and cover the area with an ice pack h for the next 4 hours. If the local reaction has then settled apply heat g for a further 24 to 48 hours. 2Possibility of local inflammation. S/C hyaluronidase may facilitate dispersion of large volume extravasations in addition to the warm compressions
Streptozocin5YYApply topical DMSO, every 2 hours at the extravasation site followed by topical hydrocortisone cream and a cold compress.1 hAvoid contact with good skin. If blistering occurs, stop the DMSO and seek further advice. Sodium bicarbonate may have a role.Surgical excision e is sometimes required to prevent serious damage
Teniposide3YYGive hydrocortisone via the venflon and sc hyrocortisone as 0.2 ml multiple injections around the circumference of the affected area, apply topical hydrocortisone and cover the area with an ice pack.2 hPossibility of local inflammation or necrosis and/or pain. There are no specific antidotes for these drugs.
Thiotepa1YYInfiltrate the site with hyaluronidase.Apply heat and compression.2 g 
Topotecan4YYInfiltrate with sodium bicarbonate into the area, followed by heat (i.e. warm compression.g)Extravasation is rareSee j
Treosulphan5YYInfiltrate with sodium bicarbonate into the area, followed by heat (i.e. warm compression.g)Extravasation is rareSee Although surgical excision e is sometimes required to prevent serious damage
Vinblastine5YYInfiltrate the area with hyaluronidase,a as 0.2 ml injections, over and around the circumference of the affected area. Apply heat and compression.5 g 
Vincristine5YYInfiltrate the area with hyaluronidase,a as 0.2 ml injections, over and around the circumference of the affected area. Apply heat and compression.5 g 
Vindesine5YYInfiltrate the area with hyaluronidase,a as 0.2 ml injections, over and around the circumference of the affected area. Apply heat and compression.5 g 
Vinorelbine5YYInfiltrate the area with hyaluronidase,a as 0.2 ml injections, over and around the circumference of the affected area. Apply heat and compression.5 g 

Further treatments for cytotoxic extravasations.

001 Give hydrocortisone via the venflon and s/c hydrocortisone as 0.2ml multiple injections around the circumference of the affected area

1. For the next 7-14 days apply DSMO every 6 hours, alternating with topical hydrocortisone cream every 6 hours (a preparation applied every 3 hours on an alternate basis)

2. Manage the situation symptomatically.

3. At 8-12 hours post incidence apply DSMO 2-hourly for the next 24 hours, and then 4 times a day for a further 10-14 days.

4. Apply warm compressions alternated with the application of topical antihistamine cream for the following three days.

5. On following days apply a topical non-steroidal anti-inflammatory cream to the affected area, four times a day for the subsequent seven days.

DMSO is normally applied topically, by painting on with a ‘cotton bud’ to the affected area four times a day for 5-7 days, it could be alternated with topical hydrocortisone. Do not use an occlusive cover. If required cover once the area is dry. Common managements for cytotoxic extravasations

Hyaluronidase : Dilute 1500 units of hyaluronidase in 2 ml of water for injection, or 0.9% sodium chloride. Gently massage the area to facilitate dispersal.

Thiosulphate : Infiltrate 1-3 ml of 3% isotonic sodium thiosulphate into the affected area using multiple ‘pin cushion’ injections. To achieve 3% sodium thiosulphate from the 50% vial in the extravasation kit, dilute 1.2ml of 50% to 20ml wiwth water for injection

Sodium Bicarbonate : Infiltrate with 1-3 ml of 2.1% sodium bicarbonate. To achieve 2.1% sodium bicarbonate from the 8.4% vial in the extravasation kit, take 5ml of 8.4% sodium bicarbonate, add 5ml of water for injection, discard 5ml of this new solution and add a further 5ml of water for injection. Caution and expert advice should be exercised, before using this antidote.

Mixture : Infiltrate the area with 1-3 ml of a100mg hydrocortisone and 10 mg chlorpheniramine upto 10 ml with water for injection. Depending upon the size it may not be necessary to use the whole 3 mls. Large-volume extravasation may need as much as 10 ml.

e Surgical excision : Moderate to severe pain persisting for 1-2 weeks after extravasation . Wide excision with use of grafts may be indicated. Inadequate excision is associated with continuing necrosis at the margins, poor granulation and failure of engraftment.

hypodermoclysis : The process of giving fluids under the skin as opposed to IV

Warm Compression W.C.C. Warm Continuous Compression. This involves applying firmly but without undue pressure a heat source (hot water bottle or small electrically heated blanket ) to the area continuously for 24 hours. The heat source should not be in direct contact with the skin and a piece of dry gauze should be laid in between. This assists the natural dispersal of the drug.

Cold Compression : P.C.C. Pulsed Cold Compress . 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 however not be placed directly on the skin and a piece of dry gauze should be laid in direct contact.

i Platinum Treatment Regime: Treatment administered within 24 hours should be ‘spread’and dilute. Injuries not treated immediately should be localise and neutral.

Acidic Extravasations : If the extravasation has been misdiagnosed or the volume extravasated wrongly assessed, the treatment could lead to an alkali extravasation. If this secondary extravasation occurs, it is far more serious and the consequence far more devastating than those associated with venous extravasation. Caution and expert advice should be exercised before proceeding with this specific management.

1 thought on “Protocol for Management of Chemotherapy Extravasations”

  1. ปั้มไลค์ says:

    Like!! Thank you for publishing this awesome article.

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