1. Extravasation of Chemotherapeutic Agents
PREPARED BY:
UMMU HABIBAH MUKHTAR
PRECEPTOR: MS GIAM WEI LI

2. Extravasation
Definition
Recognition
Treatment
Preventation

3. Is it an Infiltration or an Extravasation??
Is it a Vesicant
or an Irritant ??

4. DEFINITIONS INFILTRATION
- inadvertent administration of “nonvesicant” medication or solution into the surrounding tissue.
EXTRAVASATION
inadvertent administration of “vesicant” medication or solution into the surrounding tissue.
Difference btwn infiltration n extravasation
- Require extensive intervention
- Cause > extensive long term damage
Extravasation is different from infiltration in terms of the type and concentration of solution that enters the surrounding tissue.
Medications that can cause long-term harm or tissue
necrosis (vesicants) are associated with extravasation.
Medications that generally do not cause long-term harm or tissue necrosis (nonvesicants) are associated with infiltration.

5. TYPES OF CYTOTOXIC DRUGS
Non vesicant
Vesicant
irritant

6. 2) Kill replicating cells
VESICANT DRUGS
have the capacity to induce the formation of blisters and cause tissue destruction when extravasation occurs.
Criteria:
1) bind to DNA.
2) Kill replicating cells
3) Cause tissue or vascular dilatation
Some substances have the potential to cause tissue damage by having an osmolality greater than that of serum ( mOsmol/L) 63
When fluid leaks into tissue, the tissue is compressed because of restriction of blood flow, which decreases the amount of oxygen to the site and thus lowers the cellular pH. There is a loss of capillary wall integrity, increase in edema and, depending on severity, eventual cell death.

7. Examples of vesicant drugs
Actinomycin D
Amsacrine
Bisantrene
Daunorubicin
Doxorubicin
Epirubicine
Idarubicin
Mechlorethamine
Mitomycin C
Vinblastine
Vincristine
Vindesine
Vinorelbine

8. cause pain with or without inflammation reaction.
IRRITANT DRUGS
cause pain with or without inflammation reaction.
cause soft tissue ulcers only if a large amount of concentrated drug solution is inadvertently extravasated

9. Irritant drugs Bleomycine Plicamycin Carboplatin Streptozocin
Cyclophosphamide
Topotecan
Carmustine
Gemcitabine
Ifosfamide
Irinotecan
Melphalan
Pentostatin

10. NON VESICANT DRUGS rarely produce acute reactions or tissue damage Eg:
- asparaginase
-methotraxate
- Rituximab
do not cause long-term harm or tissue necrosis.

11. Recognizing an Extravasation
Pain at the site
Pain usually burning or stinging
Inability to flush IV catheter
Fluid leakage
Feeling of tightness
Swelling
Tenderness
Absent blood return
The extent of symptoms depends on the infusion site, condition of the tissue, concentration and volume of the vesicant, and the treatment that was applied.
Resistance on the plunger of the syringe during bolus administration

12. Figure 1. Untreated Doxorubicin Extravasation
(A) Three days after extravasation. (B) Same patient, 10 months postextravasation, after surgical debridement of the affected tissue

13. Treatment Heat and Cold Surgery Antidotes
Ulcers caused by these highly vesicant agents usually do not heal and often require plastic surgery and skin grafting.

14. 2 Approaches….. EITHER “Spread and Dilute” using: • Hyaluronidase
• Warm, continuous compression
OR “Localize and Neutralize using:
• Antidote if available
• Intermittent cold compression

15. Antidote Chemo agents Antidotes Carboplatin • Cisplatin
• Sodium Thiosulfate
• Local cooling with cold pack for 60 minutes every 8 hours.
•Cyclophosphamide
•Dacarbazine
•Oxaliplatin
Sodium thiosulfate
Dactinomycin
• Local cooling with cold pack
• Apply to site until cold
pack is no longer cool.
• Etoposide
• Vinblastine
• Vincristine
• Heat
• Hyaluronidase
Hyaluronidase is an enzyme that modifies the permeability of
connective tissue through hydrolysis of hyaluronic acid. It helps
disperse plant alkaloid vesicants that have extravasated into the
Tissue and promotes their absorption
Neutralizes a vesicant by creating an alkaline environment. The alkylating
chemotherapy agent binds to the thiosulfate instead of the tissue.
Antidotes
Two approaches dependent on extravasated agent
EITHER “Spread and Dilute” using:
• Normal Saline
• Hyaluronidase
• Warm, continuous compression and elevation of limb
OR “Localize and Neutralize using:
• Antidote if available
• Intermittent cold compression

16. Surgical (skin grafting)
Indicated
if lesion >2cm
Minimal healing 2-3 weeks after injury despite local therapeutic measure
Large extravasation from CVAD

17. Method of Administration
Monitoring the Site
Location of the Device
PREVENTION
Patients at Risk
Method of Administration
Types of Devices
Sequence of the drug
Patient Information

18. 1- monitoring the site 2- Location of the devices
Confirming venous patency
Forearm (preferrable)
Avoid limbs with impaired circulation
Avoid antecubital fossa
– risk of damage to local structure
2- Location of the devices

19. 3- Patient at risk unable to communicate chronic diseases
on medications: steroids.

20. 4- types of devices 5- sequence of the drug
Vesicants give via a newly established cannula
changing the cannula site after 24 hours
if peripheral access is difficult, CVAD is prefferable
5- sequence of the drug
Vesicants should be given first
CENTRAL VENOUS ACCESS DEVICES
often referred to as venous access ports or catheters, because they allow frequent access to the veins without deep needle sticks. Placement is usually in one of the large veins of the chest or neck, although placement can also be in the groin, if necessary. Venous access devices typically remain in place for long periods: weeks, months, or even longer

21. 6- Method of Administration
given as a slow bolus injection
e.g. vincristine must be given intravenously
repeated infusions – CVAD or PICC (preferrable)

22. 7- patient information
Inform potential problem and consequence of extravasation

23. Conclusion
The proper maintenance of intravenous lines, application of local cooling or warming for certain extravasations, and the use of antidotes to prevent the local toxic action of the extravasated drugs are the basis of medical management.

24. Reference
1.Lacy, C. A. (2009). Drug Information Handbook 18th edition. Lexi- Comp Inc. 2.Polovich, M. Whitford, J.M. & Olsen, M. (Eds.). (2009). Chemotherapy and biotherapy guidelines and recommendations for practice. Pittsburgh, PA: Oncology Nursing Society. 3.R. A. Ener, S. B. (2004). Extravasation of systemic hemato oncological therapies. Annals of Oncology 15 , 858– Schulmeister, L. (2010). Preventing and Managing Vesicant Extravasations. Journal of Supportive Oncology , Administering (Non-vesicant) Chemotherapeutic Agents By Intravenous (Iv) Push by Sarasota Memorial Hospital Nursing Procedure

25. Per St. Louis Children’s Hospital Guideline
adebamowo.com/Documents/Cancer%20Chemotherapy.pdf
chapters/Chapter%204%20Mechanisms%20of%20anticance r%20drugs.pdf
Drug Delivery in Oncology: From Basic Research to Cancer Therapy, First Edition. vch.de/books/sample/ _c01.pdf
Per St. Louis Children’s Hospital Guideline
Guideline for the Management of Extravasation