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

Extravasation Definition Recognition Treatment Preventation

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

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.

TYPES OF CYTOTOXIC DRUGS Non vesicant Vesicant irritant

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 (281-289 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.

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

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

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

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

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

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

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.

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

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

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

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

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

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

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

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

7- patient information Inform potential problem and consequence of extravasation

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.

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 , 858–862. 4.Schulmeister, L. (2010). Preventing and Managing Vesicant Extravasations. Journal of Supportive Oncology , 212-215. 5.Administering (Non-vesicant) Chemotherapeutic Agents By Intravenous (Iv) Push by Sarasota Memorial Hospital Nursing Procedure

Per St. Louis Children’s Hospital Guideline adebamowo.com/Documents/Cancer%20Chemotherapy.pdf http://www.scottbrownent.com/sample- chapters/Chapter%204%20Mechanisms%20of%20anticance r%20drugs.pdf Drug Delivery in Oncology: From Basic Research to Cancer Therapy, First Edition. http://www.wiley- vch.de/books/sample/3527328238_c01.pdf Per St. Louis Children’s Hospital Guideline Guideline for the Management of Extravasation