Management of Extravasations of Chemotherapy 1) Extravasation occurs when chemotherapy drugs leak into the surrounding tissues rather than entering the vein, and can cause damage ranging from mild skin reactions to severe tissue necrosis, depending on the drug. 2) Drugs are classified as vesicants, irritants, inflammitants, or neutrals based on their propensity to cause tissue damage. Vesicants like doxorubicin are most likely to cause damage. 3) Risk of extravasation is higher for fragile veins, elderly or ill patients, and irritating/vesicant drugs. Signs include pain, swelling, discoloration at the injection site. 4)

1. Management of Extravasations
of chemotherapy
Dr Deepak Kumar

2. Definition
• Extravasation is the inadvertent administration of drugs
into the surrounding tissues, rather than into the
intended vein. It is a serious complication of intravenous
therapy.
• A broader definition of extravasation includes the
resulting injury. Depending on the substance that is
extravasated into the tissue, the degree of injury can
range from a very mild skin reaction to severe necrosis.

3. Drug classification
Vesicants Irritants Inflammitants Neutral
Amsacrine Cisplatin Carboplatin Fluorouracil Asparginase
Carmustine Etoposide Methotrexate Bevacizumab
Dacarbazine Docetaxel Irinotecan Raltitrexed Bleomycin
Dactinomycin Teniposide Bortezomib
Daunorubicin Mitoxantrone Liposomal
Daunorubicin
Cetuximab
Doxorubicin Oxaliplatin Liposomal
doxorubicin
Cladribine
Epirubicin Topotecan Cyclophosphamid
e
Mitomycin Fludarabine

4. Drug classification
Vesicants Irritants Inflammitants Neutral
Paclitaxel Ifosfamide
Streptozocin Melphalan
Treosulfan Pemetrexed
Vinblastine Pentostatin
Vincristine Rituximab
Vindesine Thiotepa
Vinorelbine Trastuzumab
Idarubicin Cytarabine
Mustine Gemcitabine

5. Classification
• Inflammitants: drugs which are capable of causing mild
to moderate inflammation and flare in local tissues
• Neutrals: Inert or neutral compounds that do not cause
inflammation or damage

6. Risk factors
• Small fragile veins
• Multiple treatments
• Generalised vascular disease- including Raynaud’s
disease, peripheral neuropathies, peripheral vascular
disease especially in the settings of diabetes
• Age- elderly and young at more risk
• Restlessness or confusion

7. Risk factors
• Impaired lymph flow and venous circulation
• SVC (Superior vena cava) obstruction
• Insufficient patient information
• Impaired sensory perception eg. CVA

8. Other risk factors
• Insufficient training of staff, poor technique
• Organisational issues eg. Treatment delay, time pressure
• Irritant and vesicant drugs
• Previous Vinca alkaloids

9. Signs & Symptoms
• The patient complains of burning, stinging, pain or any
acute change at the injection site.
• Induration, Erythema, Venous discolouration or swelling
observed at the site
• Alteration to the rate of flow or increased resistance to
the administration of the cytotoxic medication that can
not be explained by changes in position of the body. Eg.
Bending of the wrist or elbow.

10. Signs & Symptoms
• No blood return is obtained. However, the presence of
blood return does not negate the risk of extravasation.
The needle can perforate the vein wall during vein
puncture whilst the lumen of the needle may still remain
in the vessel and allowing adequate blood flow and
return
• Leakage of fluid from around injection site.
• Bleb formation

11. Flare reactions
• Symptoms usually subside with or without treatment 30 minutes
after the infusion is stopped, although they may last for 1-2 hrs, and
rarely more than 24 hrs
Symptoms are:
• Immediate red blotches or streaks along the vein
• Local wheals along the vein
• Irritation near the site of injection
• Itching along the vein
• Localised warmth and tenderness
• Localised erythema with oedema
• Blood return still occurs with a flare reaction

12. General guidelines to
prevent Extravasation
Site
• Avoid sites on joints or bony prominences
• Do not give vesicants into the cubital fossa via a peripheral cannula
• Frequently assess the patency of the cannula during the infusion –
check for blood return during the infusion
• Do not infuse agents in areas of poor venous flow and/or poor
lymphatic drainage.
• If vein puncture is unsuccessful, make a second attempt in the
opposite arm. If the same arm must be used, choose a site proximal
to the first vein puncture and make sure it is not the same vein.

13. General guidelines to
prevent Extravasation
Cannula
• Select a small- gauge (e.g 21 gauge) cannula, either a
steel needle or a polyethylene catheter
• Ensure that the IV site can be clearly visualised
• Site and secure the cannula so it cannot become
dislodged
• Do not use butterfly needle with a vesicant drug
• Begin a new infusion for drug administration

14. General guidelines to
prevent Extravasation
• Procedure
• Administer vesicant drugs one at a time through the side arm or Y-
connection of the intravenous line.
• The line should be free flowing with brisk blood return
• When administering more than one agent- administer vesicant agents
first (unless expressly contraindicated by the administration protocol)
• Do not use an infusion pump for vesicants unless through a central
venous access device (CVAD) eg. PORT, PICC
• Observe constantly for signs of infiltration. Do not pinch the intravenous
tubing while administering the drug because it may increase the
pressure, especially in a small vein and cause extravasation leakage.
• Infuse at least 20 ml of solution after drug administration.

15. General guidelines to
prevent Extravasation
• If administering a vesicant remain with the patient for the
entire infusion
• Instruct the patient to report immediately any changes
in sensation, particularly pain, burning or stinging.

16. Extravasation Management
• Stop the infusion/ injection immediately
• Do not remove the cannula
• Disconnect the infusion.
• Connect 10 ml syringe attempt to aspirate residual
medication from the CAVD / Cannula.
• Do not exert pressure on the extravasated area
• Elevate limb and immobilise.
• Follow the instructions as per doctor

17. Extravasation Management
• Access extravasation kit
• For all drugs except the Vinca alkaloids: during the first
24-48 hrs, apply ice for 15 to 20 minutes at least 4 times
a day and elevate the extremity if it is peripheral site
• For the vinca alkaloid apply heat.
• Consider an antidote.
• If there is no antidote, remove the cannula or de-access
the CVAD

18. Extravasation Management
• Assess the site for pain, erythema, induration and necrosis
• Administer pain relief as per protocol
• Document the incident. Mark affected area or Photograph the
site if possible.
• Follow the patient closely for at least 2 weeks. Carefully
observe the site. Include an early consultation with a plastic
surgeon and if symptoms are present, with a physical
therapist.

19. Classification according to
DNA binding
• Identifying whether vesicant is Non DNA binding or DNA binding
Description Drug names Treatment
DNA-binding
vesicant drugs
Daunorubicin
Idarubicin
Amsacrine
Doxorubicin
Mithramycin
Dactomycin
Epirubicin
Mitomycin C
Dacarbazine
Mustine
Apply cold ice compress
to area for 15 minutes
q.i.d. for 48 hrs avoiding
any undue pressure
NON DNA –
binding vesicant
drugs
Vinblastine
Vincristine
Vindesine
Paclitaxel Eg. Vinca alkaloids
Apply warm compress to
area for 15 minutes q.i.d
for 24 hrs avoiding any
undue pressure.

20. Warm / Cold pack
Cytotoxics requiring warm
pack
• Inject 150 IU hyaluronidase (in
1 ml WFI) pincushion s/c
injections in 0.1 – 0.2 ml
volumes around the site
• Then
• Apply a warm pack to avoid
absorption of hyaluronidase
• Warm pack to remain in situ for
2-4 hrs after initial
management
Cytotoxics requiring cold
pack
• Cold pack + 1%hydrocortisone
cream
• Apply cold pack for 15 – 20
minutes 3-4 times a day for up
to 3 days
• Apply hydrocortisone 1%
cream tds, as long as redness
persists.
Or
• Cold pack + DMSO(Dimethyl
sulphoxide)/ dexarazoxane

21. Vesicant
Drug name Antidote Heat/ cold
Amsacrine Topical DMSO (if
blistering occurs stop
DMSO and review site)
Treat for a minimum of 7
days maximum 14 days
(4 drops/10cm2
of skin
surface)
Intermittent cold packs
Apply ice pack wrapped
in towel or cold
compresses to the
extravasation site for 1
hr. care should be taken
to avoid tissue injury
from excessive cold.
Cold causes local
vasoconstriction and
decreases fluid
absorption
Cisplatin >0.4 mg/ml
Dacarbazine
Dactinomycin
Daunorubicin
Doxorubicin
Epirubicin
Idarubicin
Mitomycin C
Mitoxantrone
Mustine

22. Vesicant
Drug name Antidote Heat / cold
Paclitaxel Administer Subcutaneous
Hyalurodinase(150 IU in 2 ml
WFI) around the area of injury
using “Pin cushion Technique”.
None recommended
Vinblastine Administer Subcutaneous
Hyalurodinase(150 IU in 2 ml
WFI) around the area of injury
using “Pin cushion Technique”.
1ml of hylourindase for 1 ml of
drug
Apply warm pack and
compress with a crepe
bandage for 24 hrs.
Care must be taken to
avoid tissue damage fron
excessive heat.
Vincristine
Vindesine
Vinorelbine

23. Irritants
Drug name Antidote Heat / cold
Liposomal Doxorubicin Do not use DMSO as
application may cause
release of active drug
from the liposomes and
result in greater damage
Intermittent cold packs
Liposomal Daunorubicin
Oxaliplatin No specific measures Intermittent Heat packs
Warm the area with a
warm pack to aid drug
dispersion
Avoid cooling as risk of
sensory neuropathies

24. Irritants
Drug name Antidote Heat / cold
Carboplatin No specific antidote Intermittent heat packs
For severe reaction apply warm packs
Care must be taken to avoid tissue
damage from excessive heat
Irinotecan
Streptozocin
Dacarbazine No specific antidote
Protect affected area
from sunlight
Intermittent heat packs
For severe reaction apply warm
packs. Care must be taken to avoid
tissue damage from excessive heat
Carmustine No specific antidote None recommended
Fotemustine
Etoposide Heat
There may be a risk of etoposide
crystallization with cooling

25. Extravasation KIT
• Hyaluronidase 1500 IU(1 ampoule)
• Hydrocortisone 1% cream – labelled with direction for use
• Sterile water for injection
• Dimethyl sulphoxide (DMSO) 99% solution 1 x 10 ml bottle with
applicator(swabsticks)
• 25 G needles
• Hot pack & Cold pack
• Spare gloves / Alcohol wipes
• Cytotoxic drug extravasation documentation form
• Patient information leaflet

26. Managing extravasation
• When doxorubin extravasates, it is recommended
to apply cool packs to the swollen area.
• When vinca alkaloids extravasate, the
recommendation is warm packs to the swollen
area.
• Physician should be notified immediately and
given specific information about the drug and drug
concentration, as well as an accurate, detailed
description of the appearance of extravasated
area.
• Subcutaneous steroid injections (?????)
• Once the infusion has extravasated, monitor the
site until tissue damage demarcation is complete.
• Assess maximum tissue damage.

27. Minimizing the risk of
extravasation

28. ESMO recommendations

29. CVAD
(Central Venous access Devices)
• Ensure patency of CVAD before commencing
administration
• The line should be free flowing with brisk blood return
• When administering chemotherapy into a CVAD,
whether via an infusion device or via gravity-flow, assess
the device patency and free-flow of the infusion at least
hourly, over the course of the infusion.

30. Questions are
welcome
Thank you