Hyaluronidase is an enzyme that breaks down hyaluronic acid, a normal component of tissue ‘cement’, and helps to reduce or prevent tissue damage by allowing rapid (within 10 minutes) diffusion of the extravasated drug (Pérez Fidalgo et al. [280]) and restoration of tissue permeability within 24–48 hours (Doellman et al. [72], INS [142]). The usual dose is 1500 international units (BNF [25]). It should be injected within 1 hour of extravasation, ideally through the intravenous device delivering the enzyme to the same tissue (Pérez Fidalgo et al. [280], Weinstein and Hagle [363]). Hyaluronidase is recommended for use with specific chemotherapy agents, specifically vinca alkaloids (Pérez Fidalgo et al. [280]; Polovich et al. [287]) and also taxanes (Pérez Fidalgo et al. [280]).

Note that hyaluronidase increases the absorption of local anaesthetic. Therefore, if local anaesthetic has been applied to the area (e.g. Ametop gel prior to cannulation) within 6 hours of extravasation, the patient should be monitored for signs and symptoms of systemic anaesthesia, such as increased pulse rate and decreased respirations, and the doctor should be informed immediately (BNF [25]).

While corticosteroids were advocated as a treatment for anthracycline extravasation in the past, due to their action on inflammatory processes, there is no evidence that tissue damage in extravasation is secondary to inflammation (Buter et al. [36]). As a result, they are not usually recommended, except in large‐volume extravasations of oxaliplatin (Pérez Fidalgo et al. [280], Polovich et al. [287]). However, given as a cream, they can help to reduce local trauma and irritation (Stanley [340]) and are often recommended in this form.

DMSO is a topically applied solvent that may improve systematic absorption of vesicants. It acts as a potent free radical scavanger that rapidly penetrates tissues and prevents DNA damage (Doellman et al. [72], Pérez Fidalgo et al. [280]). Reports on the clinical use of topical DMSO show it is effective and well tolerated in extravasation (Bertelli [23], Pérez Fidalgo et al. [280]). However, this is based on the use of a high‐dose (99%) solution, which is not always available (Pérez Fidalgo et al. [280]). Side‐effects of DMSO include itching, erythema, mild burning and a characteristic breath odour (Bertelli [23]).

Dexrazoxane (more specifically, the branded drug Savene) is a topoisomerase II catalytic inhibitor traditionally used clinically to minimize the cardiotoxicity of doxorubicin. It was first tested in animals (Langer et al. [166]) and then in a small number of patients for its use in extravasation (Doroshow [74]). It is given intravenously as soon as possible after extravasation and it appears to reduce the wound size and duration of tissue damage with anthracyclines. Triple dosage appears to be more effective than a single dose (El‐Saghir et al. [87], Langer et al. [165]). In two multicentre studies, it was shown that the administration of dexrazoxane reduced the need for surgical interventions, and late sequelae (such as pain, fibrosis, atrophy and sensory disturbance) were judged as mild (Doroshow [74], Mouridsen et al. [221]).

A consensus group (Jackson [143]) has developed recommendations for the use of dexrazoxane, and these have been further adapted by the European Oncology Nursing Society ([89]), which recommends that for anthracycline extravasations resulting from peripheral administration, the site expert or team should be consulted in order to determine whether the use of dexrazoxane is indicated. Absolute indications are if the peripherally extravasated volume exceeds 3–5 mL and in the event of a CVAD extravasation (Langer [164]). Dexrazoxane is now included in many treatment algorithms for anthracycline extravasations (Gonzalez [106], INS [142], Pérez Fidalgo et al. [280], Roe [306], Vidall et al. [359]).

Granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) is a growth factor. It is effective in accelerating wound healing and inducing formation of granulation tissue (El‐Saghir et al. [87], Ulutin et al. [357]).

It appears that most authors agree that aspirating as much of the drug as possible, as soon as extravasation is suspected, is beneficial (Polovich et al. [287], Rudolph and Larson [319], Weinstein and Hagle [363]) and can help to lower the concentration of the drug in the area (Goolsby and Lombardo [107]). However, withdrawal is only possible immediately during bolus injections, because if the drug were being delivered via an infusion, this would need to be stopped and a syringe attached in an attempt to aspirate. Aspiration may be successful if extravasation presents as a raised blister, but it may be unsuccessful if the tissue is soft and soggy (Stanley [340]). In practice, it may achieve little and often distresses the patient (Gault and Challands [104]). The likelihood of withdrawing blood, as suggested by Ignoffo and Friedman ([141]), is small and the practitioner may waste valuable time attempting this, which could lead to delay in the rest of the management procedure.

Some clinicians advocate that the peripheral vascular access device be left in situ in order to instil the antidote into the affected tissues via the device (Kassner [150], Stanley [340], Weinstein and Hagle [363]). However, others recommend that the peripheral device should be removed to prevent any injected solution increasing the size of the affected area (Rudolph and Larson [319]). There appears to be no research evidence to support either practice. It is therefore important to adhere to local institutional policies.

Cooling appears to be a better choice, with the exception of the vinca alkaloids and some non‐cytotoxic drugs, than warming (Bertelli [23], Buter et al. [36]). Cold causes vasoconstriction, localizing the extravasation and perhaps allowing time for the local vascular and lymphatic systems to contain the drug (INS [142]). It should be applied for 15–20 minutes, 3–4 times a day for up to 3 days (Polovich et al. [287], Wilkes [372]). Heat promotes healing after the first 24 hours by increasing the blood supply (Polovich et al. [287], Weinstein and Hagle [363]). It also decreases local drug concentration, increasing the blood flow, which results in enhanced resolution of pain and reabsorption of any localized swelling.

Elevation of the limb is widely recommended as it minimizes swelling (Buter et al. [36]). This can be achieved by use of a Bradford sling, but this is usually recommended when the extravasation has occurred in the hand. Gentle movement should be encouraged to prevent adhesion of damaged areas to underlying tissue (Gabriel [100], INS [142]).

It is now recognized that a plastic surgery consultation should form part of the management procedure in order to consider debridement of the affected area, although there are no standard procedures for surgical management (Boulanger et al. [28]). Surgical intervention should be considered, especially if the lesion is larger than 2 cm, if there is significant residual pain 1–2 weeks after extravasation or if there is minimal healing 2–3 weeks after injury despite local therapeutic measures (Goolsby and Lombardo [107], Pérez Fidalgo et al. [280]). A liposuction cannula can be used to aspirate extravasated material, and subcutaneous fat or a flush‐out technique can remove the extravasated drug without resorting to excision and skin grafting.

If there is little subcutaneous fat, then the saline flush‐out technique is recommended, particularly if it is done within the first 24 hours (Dionyssiou et al. [71], Gault [103]). It has been suggested as a less traumatic and cheaper procedure than surgery. Only appropriately trained doctors and nurses may perform the flush‐out technique, and it may only be used for superficial peripheral extravasations where there is no visible skin damage or extensive swelling (Dougherty and Oakley [81]). A number of small stab incisions are made and large volumes of 0.9% sodium chloride are administered, which flush out the extravasated drug (Dougherty and Oakley [81], Gault and Challands [104]) (see Procedure guideline 15.27: Extravasation: performing flush‐out following an extravasation).

Treatment is often dependent upon the severity of the infiltration. There should be ongoing observation and assessment of the infiltrated site. The presence and severity of the infiltration should be documented. Infiltration statistics should include frequency, severity and type of infusate. The infiltration rate should be calculated according to a standard formula (INS [142], RCN [295]).