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Guidelines for General Management of Cytotoxic Extravasation.

November 1992 (Revision March 1993)

The kits and instructions are available in the following places:-
Haematology Unit, Calderdale Royal Hospital,
Emergency Cupboard, Pharmacy Department, Calderdale Royal Hospital

INTRODUCTION

Recognition of Extravasation
  • Many chemotherapeutic drugs have the potential to produce severe local tissue reactions if inadvertently extravasated (delivered outside the vein) during administration. This may occur despite scrupulous venepuncture technique and careful monitoring of the infusion.
  • There are several type of local reaction which can occur, these include:-
    • a) Irritation;
    • b) Hypersensitivity (or flare) reaction;
    • c) Tissue extravasation
Suspect extravasation when
  • a) the patient complains of burning, stinging, pain or any acute change at the injection site;
  • b) induration or swelling at the injection site is observed;
  • c) no blood return is obtained or the flow rate is reduced:

The administration should be stopped immediately and extravasation should be suspected until other local reactions have been confirmed.

The seriousness of a drug extravasation relates to the inherent vesicant or irritant potential of the drug, and the rapid institution of counter measures.

 
Drugs which may be associated with Hypersensitivity Reactions
  • These include (Crisantaspase) Asparaginase, Bleomycin, Doxorubicin and Etoposide
Drugs Associated with Severe local necrosis
Commonly ---------------------------------------- Uncommonly

Vesicant

  • Daunorubicin
  • Doxorubicin
  • Epirubicin
  • Etoposide
  • Mitomycin
  • Vinblastine
  • Vincristine
  • Vindesine

Irritants

  • Carmustine

Non-vesicants

  • Crisantaspase (Asparaginase)
  • Bleomycin
  • Cyclophosphamide
  • Cytarabine
  • Fluorouracil
  • Methotrexate
General Guidelines to minimise the incidence of Cytotoxic Extravasation
  1. Cytotoxic administration should be restricted to individuals familiar with their use.
  2. The drug should be reconstituted appropriately to avoid high concentrations from being administered.
  3. The site of administration should be selected to take into account, visibility, vessel size, amount of movement and potential damage if extravasation occurs. The optimum location is usually the forearm, which has superficial veins with sufficient soft tissue to protect tendons and nerves.
  4. Insert a 23 gauge butterfly needle into the vein. A Teflon catheter may be preferred for longer duration infusions.
  5. Lightly tape the tubing in place. Do not obscure the injection site by taping.
  6. Connect a Sodium Chloride 0.9% infusion to the butterfly needle, allow about 5ml of the solution to run through, then withdraw a small amount of blood to test the vein integrity and flow. Observe for extravasation.
  7. If extravasation is obvious select another site. Avoid a distal point on the same vein.
  8. Administer the drug over at least 3 minutes; or with a large volume dose, at a rate of approximately 5ml per minute. Repeatedly ask the patient if he feels any pain or burning. For an infusion check every 2-3 minutes that it is still running.
  9. Follow the drug injection re-connect the sodium chloride 0.9 infusion, and run through at least 5ml of the solution to flush all the drug from the tubing and needle.
  10. If more than one drug is prescribed, inject the vesicant agent first, if all drugs are vesicant, inject the one with the smallest volume first. Separate each drug administration by a 3 to 5ml saline flush.

The rational behind the administration of the vesicant first is that the integrity of venous access decreases with time, therefore if vesicants are administered first, all agents can be administered.

 

General Measures for the Management of Extravasation

Minor Extravasation (not for vesicant drugs)
 
  1. Stop infusion immediately.
  2. If appropriate, the cannula can be resited proximal to the extravasation site, or preferably in another limb
  3. Cleanse the area with Sodium Chloride 0.9%.
  4. In many cases this, in combination with elevation of the limb may be the only treatment required.
More Serious Extravasation
 
  1. Stop the injection immediately, DO NOT remove the needle (or cannula). This retains the pathway to the infiltrated tissue, and reduces the need for multiple punctures.
  2. With the needle in place, try to withdraw any solution from the site of infiltration, if this is not possible, inject 3 to 4ml of sodium chloride 0.9% through the needle, and withdraw the solution.
    • If the needle (or cannula) has been removed, remove some of the extravasated drug by needle aspiration of any obvious fluid swelling, or if possible gently expressing any fluid out of the swelling via the injection site, then clean the skin area with sodium chloride 0.9%.
  3. Dilute the drug and its harmful effects by infusing about 5 to 10ml of sodium chloride 0.9% injection through the line into the infiltrated tissue.
    • If the needle (or cannula) has been removed. infuse 5ml of sodium chloride 0.9% for injection by multiple intradermal and sub-cutaneous injection with a fine bore needle.
  4. Inject a specific antidote, if available (see later), through the existing line.
    • If no specific antidote is available, 100-200mg Hydrocortisone may be infused through the existing line, and small volumes of 0.1 to 0.2ml Hydrocortisone Injection (100mg in 1ml) injected around the circumference of the area of extravasation. If the needle (or cannula) has been removed, the hydrocortisone can be given by multiple intradermal or subcutaneous injection using a fine hypodermic needle
    • NB Corticosteroids should not be used after extravasation by Vinca Alkaloids as this may increase tissue damage
  5. Remove the needle (or cannula) if still in place.
  6. Cleanse the area with sodium chloride 0.9%.
  7. Where possible, elevate the extremity and minimise swelling and/or encourage movement.
  8. Apply Hydrocortisone Cream 1% twice daily to the affected area for as long as the erythema persists.
  9. Where Sodium Bicarbonate is suggested as an antidote, it should be diluted by withdrawing 5ml of the 4.2% solution and making up to 10ml with Water for Injection, this makes a final concentration of 2.1%. No more than 5ml of this solution needs to be injected.
  10. Application of heat or ice-pack?
    • It appears that these may be of benefit for certain drugs, see table.
    • Application of heat induces vasodilation, increasing drug distribution and absorption. Moist heat, however, may lead to maceration.
    • Application of cold tends to cause local vasoconstriction and allow the localisation of the drug to the immediate area of extravasation. Cooling may reduce the uptake of the drug into cells. Cold compresses cannot be applied for too long without causing tissue damage due to freezing. For the first 24 hours use a cold pack intensively. Apply a cold pack for 20 minutes, remove and repeat as soon as possible for 24 hours. An alternative method is to apply the cold pack 3 or 4 times daily until the swelling and pain settle.
  11. With epirubicin, daunorubicin, doxorubicin and IV mitomycin, apply alternate applications of Dimethylsulphoxide (DMSO) 99.9% solution and 1% hydrocortisone cream. The DMSO should be applied to the area using a cotton wool ball and the solution allowed to evaporate. Wear gloves whilst applying the DMSO solution.
    • Start with the DMSO, 2 hours later apply the 1% hydrocortisone cream. After a further 2 hours, re-apply the DMSO again and continue alternating the applications every 2 hours for 24 hours.
    • If the area is still red and painful, continue the applications of DMSO and hydrocortisone cream, painting on the DMSO, let it evaporate, the apply the hydrocortisone cream four times a day.
    • If the area feels better, or there is no change, carry on with the DMSO four times a day for 14 days.
    • If blistering occurs due to the DMSO, discontinue use.
    • If the area affected is large, intensive therapy can be continued for 48 hours.
  12. Record all action taken (on the green card provided) by Nurses, Doctors and Pharmacists. Make the appropriate notes in the Nursing Kardex, and Patients Case Notes. Return the Green Card to the Pharmacy Department. (Anonymity will be maintained).
  13. Arrange follow-up examinations, to observe the area daily, and report any increased discomfort, peeling or blistering of the skin.
  14. If a slough forms, refer for plastic surgery as healing will be very slow and the site may act as a reservoir for infection.
  15. The use of 'Mega Pulse' (contact the Physiotherapy Department) may be of benefit. This may require follow-up on a daily basis depending on severity.

 

Degree of Irritation Management Antidote Further Information
Bleomycin Very mild No specific treatment necessary - follow general guidelines
-
Bleomycin is well tolerated in tissues
Carmustine Severe Follow the guidelines, using hydrocortisone injection, application of ice or cold pack and hydrocortisone cream Injection of no more than 5ml sodium bicarbonate 2.1% through the existing line
-
Cyclophosphamide Non-irritant No specific treatment necessary - follow general guidelines
-
Cyclophosphamide is inert until activated by liver enzymes
Cytarabine Mild Following the guidelines, using hydrocortisone injection, application of ice or cold pack and hydrocortisone cream
-
These measures may not always be necessary
Daunorubicin Severe Follow general guidelines, using hydrocortisone injection, application of ice or cold pack. Alternate applications of dimethylsulphoxide solution and hydrocortisone have been seen to be beneficial, the DMSO being applied four times a day for 14 days - see general measures 11. Injection of no more than 5ml of sodium bicarbonate 2.1% through the existing line
-
Doxorubicin Severe As for daunorubicin As for daunorubicin
-
Epirubicin Severe As for daunorubicin As for daunorubicin
-
Etoposide Mild to moderate Follow general guidelines, using hydrocortisone injection, application of ice and cold pack and hydrocortisone cream
-
-
Fluorouracil Non-irritant No specific treatment necessary - follow general guidelines
-
-
Methotrexate Non-irritant No specific treatment necessary - follow general guidelines
-
-
Mitomycin Severe Inject up to 5ml sodium bicarbonate 2.1% sub-cutaneously into the area, followed by hydrocortisone injection. Apply ice or cold pack as in general guidelines. Alternate application of DMSO and hydrocortisone have been shown to be beneficial (continue DMSO qds for 14 days.) Injection of no more than 5ml sodium bicarbonate 2.1% through the existing line Systemic injection of vitamin B6 may help to promote regrowth of damaged tissue
Mitozantrone Mild No specific treatment necessary - follow general guidelines
-
-
Vinblastine and Vincristine Moderate to severe Dissolve the hyaluronidase (1500 units) in 20ml sodium chloride. Then inject 2ml (150units) of the solution in a pin cushion fashion into the area of extravasation. Local injection of hyaluronidase and the application of moderate heat to the area of leakage help to disperse the drug, and are thought to minimise discomfort and possibility of cellulitis.
-
-