EXTRAVASATION

Dr. Almaja Lekshmi

DEFINITION

When a healthcare professional administers a drug through a venous

cannula, there is a small risk of the solution leaking out of the veins
and into the surrounding tissue.

The leakage of an anticancer drug from a blood vessel or

tube into the tissue around it.
When the leakage is not of harmful consequence it is known as infiltration.
CLASSIFICATION OF ANTINEOPLASTICS
Based on their risk for tissue damage

● Non-irritant: antineoplastics with no tissue aggression potential.

● Low-risk irritant: antineoplastics that can cause local irritation that may be
associated with pain, a burning sensation or pressure, with or without signs
of local inflammation and phlebitis, both at the injection site and along the
vein.
● High-risk irritant: antineoplastics that can cause damage associated with
confirmed cases of lesions compatible with vesicant damage.
● Vesicant: antineoplastics that may cause local or extensive tissue necrosis,
with or without ulceration, and complete loss of skin thickness and
underlying structures.
VESICANTS : Vesicant drugs are also classified into 2 groups: DNA binding and non-DNA binding.

DNA binding Non-DNA binding

➢ Alkylating agents: ➢ Taxanes:
• Nitrogen mustard
• Docetaxel • Paclitaxel
➢ Anthracyclines:
DNA binding
• Daunorubicin • Doxorubicin
•Epirubicin • Idarubicin ➢ Vinca alkaloids:
➢ Antitumor antibiotics: • Vinblastine • Vincristine
•Dactinomycin • Mitomycin-C •Vinorelbine • Vindesine
IRRITANTS

➢ Alkylating agents

• Bendamustine • Carboplatin • Carmustine • Cisplatin • Cyclophosphamide

•Dacarbazine • Ifosfamide • Melphalan • Oxaliplatin

➢ Antimetabolites

• Cytarabine • Fludarabine • 5-fluorouracil • Gemcitabine • Methotrexate

➢ Other

• Bleomycin • Bortezomib • Carfilzomib • Dexrazoxane • Etoposide •Ipilimumab •

Irinotecan • Liposomal doxorubicin • Mitoxantrone • Nivolumab • Topotecan
RISK FACTORS
● If the administration of the drug is too quick, poor injection or cannula
technique
● Obstruction in the IV line

Risk factors can be classified under patient-related, procedure-related, and product-

related factors.
Patient-related factors
- Small and fragile veins in infants, children, or elderly patients

- Vessels that may burst easily

- Cancer patients with hardened and thickened vessels due to frequent venipuncture

- Patients with vessels that move easily during venipuncture attempts

- Patients with excised lymph nodes, limb amputation

- Obesity in which peripheral venous access is more difficult

- Patients who move around a lot

Procedure-related factors

- Untrained or inexperienced staff

- Multiple attempts at cannulation

- High flow pressure

Product related factors

- Inadequate choice of equipment (peripheral catheter choice, size, or steel

needle)

- Inadequate dressings

- Poor cannula fixation

-The medication is very acidic or basic (5<pH>9)

-Drugs that cause the vein to constrict or spasm

● Direct cellular toxicity - including concentration and volume extravasated of
the medication: Cisplatin is classified as a vesicant in doses greater than 0.4
mg/mL and as a high-risk irritant in concentrations lower than 0.4 mg/mL
● Whether a therapy is a DNA-binding or non–DNA-binding vesicant.

DNA-binding vesicants, such as anthracyclines, amsacrine, dactinomycin and

mitomycin, are absorbed locally and cause apoptosis of cells. They are not
metabolized, and they are liberated again in the extracellular space and also
can destroy healthy cells. They produce continuous, chronic and progressive
tissue damage.

Non-DNA-binding vesicants, such as vinca alkaloids, have less necrotizing

capability.
SIGNS AND SYMPTOMS
➢ Acute
● Erythema
● Feelings of coolness around
site
● Infusion slows or stops
● Pain, burning, stinging
● Swelling at site
➢ Delayed
● Blistering, ulceration
● Discoloration
● Dry desquamation, peeling and sloughing
of skin
● Functional impairment
● Increased erythema
● Increased pain
● Necrosis, eschar formation
● Sensory impairment at site of
extravasation
SEVERITY - GRADES

GRADE I : A mild case of extravasation

● Discomfort or pain around the needle site

● Medication not passing through the cannula as easily
● A minimal amount of swelling without skin discoloration
GRADE II : More serious than grade one and involves additional symptoms

● Slightly more pain around the needle site

● Medication flowing more slowly through the cannula
● Mild swelling
● Slight redness
GRADE III : Symptoms include:

● Strong pain around the needle site

● Blocked cannula
● Swelling
● Skin paler or more gray than usual, with or without nearby discoloration

Pallor can be difficult to detect in dark skin, so healthcare professionals may check
the eyes, palms, and nail beds for signs of discoloration.
GRADE IV :

● Intense pain around the injection or needle site

● Prominent swelling
● Patches of paler skin that are cool to the touch, possibly with areas of darker-
than-usual skin nearby
● Blistering

GRADE V : Death
 0 1 2 3 4
Color Normal Pink Red Blanched Blackened
Integrity Unbroken Blistered Superficial skin Tissue loss Tissue loss
loss exposing exposing
subcutaneous muscle/bone
tissue with a deep
crater or
necrosis

Skin Normal Warm Hot

temperature
Edema Absent Non-pitting Pitting
Mobility Full Slightly limited Very limited Immobile

Pain Rate on a scale of 0–10

Fever Normal Elevated (highest value during 24 hours)
MANAGEMENT

1. Stop the infusion and leave the cannula in place. (Put on sterile gloves)
2. Remove as much of the drug as possible using a 10–20-milliliter syringe
(connected to the cannula). Slowly aspirate back blood back from the arm,
preferably with as much of the infusion solution as possible.
3. Alleviate any pressure on the affected area.
4. If there are blisters on the arm, aspirate content of blisters with a new thin
needle
5. Take out the cannula and mark the affected area with a pen.

6. Alert a doctor if they have not done so already so that treatment can begin.

7. Elevate patient’s extremity.

8. Administer pain relief if the person needs it.

9. Monitor the area for infection or further tissue injury progression.

● Measure and document the area of edema or erythema.
● Photograph the area and document with the date and time stamp within the
picture.
A photograph allows for continuity of care between practitioners, as well as
thorough documentation.

● Depending on the type of drug that has leaked into the tissue, doctors may
warm or cool the affected area to stop the drug from spreading.
● If, for the extravasated medication, substance-specific measures apply, carry
them out (e.g. topical cooling, DMSO, hyaluronidase or dexrazoxane may be
appropriate).
WARM AND COLD COMPRESSION
● Generally cold compresses are recommended for extravasation of all irritant
and vesicant drugs except vinca alkaloids (vincristine, vinblastine,
vinorelbine), epipodophyllotoxins (etoposide), oxaliplatin, and vasopressors,
as cold worsens tissue ulceration caused by these drugs.
● Cold compresses cause vasoconstriction, limiting the spread of the
extravasated drug. Additionally, cold reduces local inflammation and pain.
● Warm compresses are preferred for extravasation of specific drugs including
vinca alkaloids, etoposide, vasopressors, and oxaliplatin to increase local
blood flow and enhance drug removal.
● Apply compresses for 20 to 60 minutes 3 or 4 times daily for the first 24 to 72
hours after extravasation occurs.
 ANTIDOTES
Vesicant agent Antidote Local treatment
Alkylating agent (nitrogen mustard) Sodium thiosulfate Cooling pack
Extremity elevation
Anthracyclines (daunorubicin, Dexrazoxane Cooling pack
doxorubicin, epirubicin, idarubicin) Extremity elevation
Antitumor antibiotics NA Cooling pack
(dactinomycin, mitomycin C)
Plant alkaloids (vinblastine, Hyaluronidase Heating pack
vincristine, vindesine, vinorelbine) Extremity elevation
Alkylating agent:
Give sodium thiosulfate as prescribed.
i. Administer sodium thiosulfate immediately after extravasation.
ii. Inject 2 ml of the antidotal solution (with a 25-G or smaller needle) for each
milligram of mechlorethamine extravasated.
Sodium thiosulfate neutralizes nitrogen mustard extravasation to form non-toxic
thioesters that are excreted in urine.
Anthracyclines:
Administer dexrazoxane intravenously as prescribed within 6 hours of
extravasation or as soon as possible.
Systemic dexrazoxane treatment prevents anthracycline-induced wound formation
by binding to iron and preventing the formation of free radicals.
i. Apply ice over tissue that is extravasated with an anthracycline.

ii. Remove ice 15 minutes before initiating the dexrazoxane treatment to allow blood flow
to the area of extravasation.

iii. Administer a daily dexrazoxane dose of 1000 mg/m2 intravenously over 1 to 2 hours;
then on the third day, administer one dose of 500 mg/m2 within 24 hours for a total of 3
days.

iv. Administer dexrazoxane intravenously away from the extravasation site (e.g., on the
opposite arm).

v. Monitor the complete blood count, including granulocyte and platelet counts, and liver
enzyme levels.

Bone marrow suppression and elevated liver enzyme levels are potential side effects of
dexrazoxane.
Vinca alkaloids and microtubule inhibitors:

Administer hyaluronidase as prescribed.

Hyaluronidase degrades hyaluronic acid, promotes drug diffusion, and enhances drug
absorption.

i. Inject about 0.2 ml (1 to 6 ml of a 150 unit/ml solution) subcutaneously (25-G needle)

in a clockwise manner around the extravasation site in five injections.

ii. The usual dose is 1 ml of hyaluronidase solution for every 1 ml of extravasated agent.

Antitumor antibiotics (e.g., mitoxantrone, an irritant with vesicant properties):

No known antidote is available. Care includes ice pack application for 15 to 20 minutes
at least four times a day for the first 24 hours
Vesicant or Irritant Administration with Suspicion of Extravasation

● Schedule the patient for follow-up assessments of the site at, minimally, 24
hours, 48 hours, and 1 week after the extravasation, preferably by the same
practitioner or nurse.
● Follow-up should continue for at least 3 weeks or until complete resolution of
the extravasated site.
● Photograph the site at each assessment.
● Document the site’s appearance, the patient’s reports, and functional changes
at each assessment.
● Instruct the patient to keep the affected extremity elevated.
PREVENTION
● Implement standardized, evidenced-based techniques when inserting
cannulas
● Avoiding inserting needles into joints or areas that are difficult to secure
● Choosing a different IV route or alternative vein if possible
● Removing and resecuring a cannula if it seems unstable
● Looking out for swelling when administering medication
● Asking a person if they feel any pain when administering a medication or
solution
● Delivering drugs at the correct rate
● Checking for blood flowing backward through the cannula
● Choose a large, intact vein with good blood flow for the venipuncture and
placement of the cannula. Place the smallest gauge and shortest length
catheter to accommodate the infusion.
● The infusion should consist of a suitable carrier solution with an appropriately
diluted medicinal/chemotherapy drug inside.
● After the IV infusion has finished, flush the cannula with the appropriate fluid.
● Ensure that the extravasation kit, antidote, and spill kit are accessible.
DOCUMENTATION
(1) Patient name and number

(2) Date and time of the extravasation

(3) Name of the drug extravasated and the diluent used (if applicable)

(4) Signs and symptoms (also reported by the patient)

(5) Description of the IV access

(6) Extravasation area (and the approximate amount of the drug extravasated)

(7) Management steps with time and date

EXTRAVASATION KIT
● Instructions for use
● 3 x 10 mL syringes
● 3 x 5 mL syringes
● Blunt drawing up needles
● 4 x 25 or 27 gauge needles
● 4 x 5 mL sterile water for injection
● 4 x 10 mL sodium chloride 0.9%
● 2 x 20 mL dimethyl sulfoxide
(DMSO) 99% solution
● Glass dropper or cotton buds/swab
sticks for DMSO 99% solution
application
● 2 x vials hyaluronidase 1500
International Units
● Gauze squares (assortment of
sizes)
● Chemoprotectant gloves
(assortment of sizes)
● Alcohol wipes
● 2 hot packs for warm compresses
● 2 cold packs for cold compresses
● 2 x disposable paper tape measure
● permanent marker pen