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Evidence‐based approaches

Extravasation is a well‐recognized complication of intravenous chemotherapy administration, but in general is a condition that is often underdiagnosed, undertreated and under‐reported (Stanley [340]). Estimates of the incidence of extravasation vary between 0.5% and 6% of all cytotoxic drug administrations (Goolsby and Lombardo [107], Kassner [150], Khan and Holmes [154], Lawson [170], Masoorli [187]), but some estimates of the incidence of peripheral extravasation are between 23% and 25% (Roth [307]). Compilation of such figures is problematic, however, due to the lack of any centralized reporting or nationally or internationally agreed parameters, rendering it difficult to obtain true figures (Pérez Fidalgo [280]). There are no available figures for the incidence of non‐neoplastic vesicant extravasations (Buter et al. [36]).

There appears to have been a reduction in the incidence of extravasation with the increased use of central venous access devices (CVADs) in chemotherapy administration (Buter et al. [36]), although the incidence is estimated to still be up to 6% with ports (Masoorli [187]). However, when extravasation does occur alongside the use of a CVAD, the severity of the injuries can be greater than with the use of a port due to delayed detection (Kassner [150], Polovich et al. [287], Stanley [340]) and the site of the CVAD (Pérez Fidalgo et al. [280]).

Even when practitioners have many years of experience, extravasation of vesicant agents can occur and is an extremely stressful event for both patient and practitioner. However, it is not in itself an act of negligence by the practitioner (Weinstein and Hagle [363]).

Early detection and treatment are crucial if the consequences of an untreated or poorly managed extravasation are to be avoided (Box 15.16 and Figure 15.41). However, the initial signs and symptoms of an extravasation may be subtle, and, while they usually occur immediately, there can be a delay of up to 1–2 weeks before they appear (Susser et al. [343]). Signs and symptoms may include (Polovich et al. [287]):

blistering (typically occurs 1–2 weeks post‐extravasation)
peeling and sloughing of the skin (about 2 weeks post‐extravasation)
tissue necrosis (2–3 weeks post‐extravasation) with resulting pain
damage to tendons, nerves and joints
functional and sensory impairment of affected area, such as limb disfigurement (Polovich et al. [287]).

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Figure 15.41 Extravasation.

These can all result in hospitalization and plastic surgery, delay in the treatment of disease, lifelong disability and psychological distress for the patient.

Box 15.16

Considerations for the prevention of extravasation

Monitoring the site
Location of the device
Identification of patients at risk
Sequence of drugs
Types of devices
Method of administration
Skill of practitioner
Informing the patient of early signs and risks

Before administration of any vesicant drugs, the nurse should know which agents are capable of producing tissue necrosis; damage is usually caused by the ability to bind to DNA, or the pH, osmolarity or vasoconstrictive nature of the drugs (Table 15.15). Drugs should not be reconstituted to give solutions that are higher in concentration than is recommended by the manufacturer, and the method of administration (e.g. infusion or injection) should be checked. If in any doubt, the drug data sheet should be consulted; if this information is insufficient, the pharmacy department should be contacted regarding the action to take if a vesicant drug extravasates. Consideration should be given to the management of mixed vesicant drug extravasation in terms of which drug to treat with which antidote. For example, if drug A and drug B were in the same infusion and they required different antidotes, but drug A would cause more damage than drug B, the correct action would be to use the antidote for drug A (How and Brown [131]). Possible causes of extravasation are shown in Table 15.16.

Table 15.15 Examples of vesicant cytotoxic and non‐cytotoxic drugs in common use

Group A drugs	Group B drugs
Vinblastine Vindesine Vinorelbine Vincristine Vinflunine Paclitaxel Calcium chloride Calcium gluconate Phenytoin Hypertonic solutions (e.g. sodium chloride >0.9%) Sodium bicarbonate (>5%) Glucose 50%	Amsacrine Carmustine (concentrated solution) Dacarbazine (concentrated solution) Dactinomycin Daunorubicin Doxorubicin Epirubicin Amrubicin Actinomycin D Mitomycin C Idarubicin Mechlorethamine Streptozocin Aciclovir Amphotericin Cefotaxime Diazepam Ganciclovir Mannitol Potssium chloride (>40 mmol/L) Potassium phosphate Thiopental

Table 15.16 Possible causes of extravasation

Peripheral devices	Central venous access devices
Vein wall puncture or trauma Dislodgement of the cannula from the vein Administration of a vesicant in a vein below a recent venepuncture or cannulation site (<24 hours)	Perforation of the vein Catheter leakage, rupture or fracture Separation of the catheter from the portal body of an implanted port Incomplete insertion of needle into an implanted port Needle dislodgement from an implanted port Fibrin sheath – leading to backflow of drug along the catheter from the insertion site

Source: Adapted from Mayo ([188]), Polovich et al. ([287]), Schulmeister ([327]).

Methods of preventing infiltration and extravasation

The nurse's focus should be on safe intravenous technique and implementing strategies to minimize risk (Weinstein and Hagle [363]). These include the following considerations.

Patients at risk

Patients who are at increased risk of extravasation (Box 15.17) should be observed particularly closely and cared for with extra caution.

Box 15.17

Patients at risk of extravasation

Infants and young children
Elderly patients
Patients who are unable to communicate, due to sedation, unconsciousness, confusion or language issues
Patients with chronic diseases, for example cancer, peripheral vascular disease, superior vena cava syndrome or lymphoedema
Patients on anticoagulants or steroids
Patients who have undergone repeated intravenous cannulation or venepuncture
Patients with fragile veins or who are thrombocytopenic
Obese patients, due to increased difficulty in locating and palpating a vein, and reduced ability to observe any swelling
Malnourished patients
Patients with skin disorders such as eczema or psoriasis
Restless patients

Source: Adapted from Goolsby and Lombardo ([107]), Polovich et al. ([287]), Sauerland et al. ([322]), Wilkes and Barton‐Burke (2011).

Types of device

The use of steel needles is associated with a greater risk of extravasation and should be discouraged; a plastic cannula should be used instead (INS [142], Polovich et al. [287], Rodrigues et al. [304], Sauerland et al. [322]). Vesicants should be given via a newly established cannula wherever possible (Dougherty [79], Goolsby and Lombardo [107]) and consideration should be given to changing the cannula site after 24 hours (Wilkes [372]).

However, if the fluid runs freely, there is good blood return, and there are no signs of erythema, pain or swelling at the site, there is no reason to inflict a second cannulation on the patient (Weinstein and Hagle [363]). Consideration should be given to use of a CVAD if peripheral access is difficult; a decision‐making tool can assist with this, for example the Vessel Health and Preservation tool (Hallam et al. [114]) – see Chapter c17: Vascular access devices: insertion and management.

Location of the device

The most appropriate site for a peripheral cannula is considered to be the forearm (Pérez Fidalgo et al. [280], Polovich et al. [287], Weinstein and Hagle [363]). However, a large, straight vein over the dorsum of the hand is preferable to a smaller vein in the forearm (Weinstein and Hagle [363]). Siting over joints should be avoided as tissue damage in this area may limit joint movement in the future. It is also recommended that the antecubital fossa should never be used for the administration of vesicants because of the risk of damage to local structures such as nerves and tendons (Gabriel [100], Weinstein and Hagle [363]). Avoid venepuncture sites in limbs with impaired circulation, sclerosis, thrombosis or scar formation. Also avoid cannulation below a recent venepuncture site (Goolsby and Lombardo [107]). Use of the ipsilateral limb in women post‐mastectomy is controversial, but it can be considered where lymphoedema is absent (Pérez Fidalgo et al. [280]).

Sequence of drugs

While there is some variation in opinion on the optimal order of administration (Table 15.17), vesicants should be administered first (Goolsby and Lombardo [107], Wilkes [372]).

Table 15.17 Drug sequencing: rationales for administering vesicant drugs first or last

Vesicants first	Vesicants last
Vascular integrity decreases over time Vein is most stable and least irritated at start of treatment Initial assessment of vein patency is most accurate Patient's awareness of changes will be more acute at the start of treatment	Vesicants are irritating and increase vein fragility Venous spasm may occur and mask signs of extravasation

Source: Adapted from Weinstein and Hagle ([363]), Wilkes ([372]).

Methods of administration

Many vesicants must be given as a slow bolus injection, often via the side arm of a fast‐running intravenous infusion of a compatible solution, for example doxorubicin or epirubicin via an infusion of 0.9% sodium chloride. If repeated infusions are to be given then use of a CVAD may be appropriate (Stanley [340], Weinstein and Hagle [363]).

Monitoring the site and early recognition of extravasation

Confirm venous patency by flushing with 0.9% sodium chloride solution with at least 5–10 mL prior to administration of vesicants and monitor frequently thereafter (Goolsby and Lombardo [107], Weinstein and Hagle [363]). Checking blood return after every 2–5 mL is recommended but cannot be relied upon as the key sign when giving a bolus injection; monitor the site every 5–10 minutes for any swelling (Weinstein and Hagle [363]).

It is important that the nurse does not rely on infusion pumps to raise an alarm about downstream occlusion and alert them to an infiltration or extravasation (Huber and Augustine [132], INS [142], Marders [184]) (Table 15.18 and Box 15.18).

Table 15.18 Nursing assessment of extravasation

Assessment parameter	Flare reaction	Venous irritation	Immediate manifestations of extravasation, i.e. during drug administration	Delayed manifestations, i.e. from 24 hours after extravasation
Pain	None	Aching, throbbing sensation along vein and in the limb	Severe stinging or burning pain (not always present); this can last from minutes to hours and will eventually subside; occurs during drug administration at the device site and surrounding areas	Can continue following extravasation or start within 48 hours; pain may intensify over time
Redness	Immediate blotches or tracking along the vein; this will subside within 30–45 minutes with or without treatment (usually steroid cream)	Vein may become red or darkened	Not always present immediately; more likely to see blanching of the skin; as the area becomes inflamed, redness will appear around the device site	Later occurrence
Swelling	Unlikely	Unlikely	May occur immediately but may not always be easy to identify immediately	Usually within 48 hours
Blood return	Usually present	Usually present and may require application of heat to improve blood return	Inability to obtain blood return (peripheral or central) but blood return may be present throughout	None
Ulceration	Unlikely	Unlikely	Unlikely	Can occur within 48–96 hours but may take 3–4 weeks to develop
Others	Urticaria	None	Change in quality of the infusion or pressure on the syringe	Local tingling and sensory deficits

Box 15.18

Signs and symptoms of extravasation

The patient complains of burning, stinging pain or any other acute change at the injection site, although this is not always present (Polovich et al. [287], Wilkes [372]). This should be distinguished from a feeling of cold (which may occur with some drugs) or venous spasm (which can be caused by irritation and is usually accompanied by pain described as an achiness or tightness) (Wilkes [372]). Any change of sensation warrants further investigation (Goolsby and Lombardo [107]).
Swelling is a common symptom (Polovich et al. [287]). Induration or leakage may also occur at the injection site. Swelling may not always be immediately obvious if the patient has the cannula sited in an area of deep subcutaneous fat or in a deep vein, or if the leak is via the posterior vein wall (Dougherty [78]).
Blanching of the skin occurs (Terry [347]). Erythema can occur around the injection site but this is not usually present immediately (Wilkes [372]). It is important that this is distinguished from a flare reaction (Polovich et al. [287]).
Blood return is one of the most misleading of all signs, particularly related to peripheral devices. In peripheral devices, if blood return is sluggish or absent, this may indicate lack of patency or incorrect position of the device. However, if no other signs are apparent, this should not be regarded as an indication of a non‐patent vein, as a vein may not bleed back for a number of reasons and extravasation may occur even in the event of good blood return as the device may still be in the vein but the leak may be in the posterior vein wall (Wilkes [372]). Any change in blood flow should be investigated (Weinstein and Hagle [363], Wilkes [372]). In central venous access devices, there should always be blood return; if this is absent, steps should be followed to verify correct tip and needle position or resolve a fibrin sheath (see Chapter c17: Vascular access devices: insertion and management and Figure 17.4).
A resistance is felt on the plunger of the syringe if drugs are given by bolus (Stanley [340]).
There is absence of free flow when administration is by infusion, once other reasons have been excluded, for example position (Polovich et al. [287], Stanley [340]).
There is leaking around the intravenous cannula or implanted port needle (Polovich et al. [287]).

Note: one or more of the above may be present. If extravasation is suspected or confirmed, the injection or infusion must be stopped immediately and action must be taken (INS [142], Polovich et al. [287], Weinstein and Hagle [363]).