October 2017
clinical initiatives, research and current updates in treatment
Treatment of Chemotherapy Extravasation Patrick Cullen, Pharmacy Practice Unit Extravasation is the escape of fluid into the extravascular space, either by leakage from a blood vessel or direct infiltration.1,2 The term usually refers to intravenous (IV) medication infiltrating the tissue around a blood vessel, which can cause injury ranging from mild skin reaction to severe necrosis.3 Extravasation is of particular concern with antineoplastic agents, as the basis for their mechanism of action usually depends on causing deliberate cellular toxicity. The incidence of chemotherapy extravasation is unclear. Estimated rates of extravasation of chemotherapy range from 0.01% to >5% per patient treated.4,5 Some data suggests that the incidence is decreasing, most likely due to increased awareness, and improved infusion guidelines and techniques.6,7 A number of factors may contribute to the risk of extravasation. These can be classified into mechanical factors relating to catheter insertion and placement, physiological factors relating to vascular problems, and the pharmacologic characteristics of the infused drug.8 Some of these factors are listed in Table 1. Patients receiving chemotherapy often have
one or more risk factors for extravasation. For example they tend to be older, meaning they are more likely to have fragile, thin and/or mobile veins.3 Chemotherapy extravasation can cause a wide range of symptoms, which vary according to the amount or concentration, and nature of the extravasated drug. Agents are separated into three broad categories on the basis of their mechanisms of cellular damage and potential to cause tissue injury: vesicants, irritants, and non-vesicants.6,8 Refer to Table 2. Note that some irritants may act like vesicants if a large volume or high concentration is extravasated. Non-vesicants rarely produce a reaction, but for other agents initial symptoms occur immediately after extravasation. There is usually acute pain (from mild to intense), and, within hours, this is usually followed by erythema and oedema surrounding the injection site. Initial symptoms are usually similar no matter the causative agent, however the progression beyond these initial symptoms differs greatly between irritants and vesicants.6,10,11 Irritants usually cause only a mild inflammatory reaction as described above.
Symptoms are usually of short duration and long-term effects are rare. Vesicants, on the other hand, have the potential to cause severe and lasting injury. Tissue destruction may be progressive and slow, taking weeks to manifest. This can progress to ulceration and even necrosis, which may damage underlying structures such as nerves, muscles and joints. Occasionally the damage may be so severe that function cannot be recovered in the affected area.6,8,10 Of the vesicants, anthracyclines have the greatest potential for injury. This is due to their mechanism of action. Drugs that bind nucleic acids in DNA (e.g. anthracyclines) cause cell death and lysis, which allows the drug to affect surrounding cells. This repetitive process can result in progressive and chronic tissue injury. Drugs which don’t bind to DNA can potentially be metabolised and cleared, limiting tissue injury. Because of the extent of injury which they can cause, and because they are in widespread use, anthracyclines are one of the most important chemotherapy agents to consider with regards to extravasation. Continued on page 4.
Table 2. Examples of common chemotherapeutic agents and classification.6
Table 1. Some key risk factors for extravasation.8,9 Mechanical
Pharmacological
Physiological
Vesicants
Irritants
Non-Vesicants
Small/fragile/ mobile veins
Vasoconstrictive potential
Impaired circulation
Anthracyclines (e.g. doxorubicin, epirubicin)
Etoposide, Bortezomib, Gemcitabine Platinum salts (carboplatin, cisplatin, oxaliplatin) Irinotecan, Fluorouracil Taxanes (e.g. docetaxel, paclitaxel)
Bleomycin
Poor cannulation site Untrained/inexperienced staff Bolus injection
High flow pressure
pH & osmolarity (further from physiologic levels increases the risk)
Decreased sensation (e.g. neuropathy)
Pre-existing conditions (e.g. diabetes)
Vinka alkaloids (e.g. vincristine, vinblastine) Mitomycin
Cytarabine Pemetrexed Monoclonal antibodies