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Managing chemotherapy extravasations in practice

Chemotherapy extravasations are a known potential risk associated with chemotherapy administration and one that professionals must know how to minimise, recognise and manage appropriately

Helen Roe MSc
Consultant Cancer Nurse
North Cumbria University Hospitals 
NHS Trust
An extravasation is a serious risk associated with receiving chemotherapy and yet there has historically been little published evidence relating to the incidence and management. Often evidence focuses on small patient numbers or a specific management strategy.1 Although there are European and National recommendations, along with all organisations requiring management guidelines there remains no clear management pathway that includes all options.2,3
What is an extravasation? 
Chemotherapy drugs act on cells that divide rapidly (cancerous and non-cancerous) during the cell cycle by damaging the ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) of the cell, aiming to prevent the cancer cells from dividing. They are classed as either cell cycle specific, that is, they only work on certain parts of the cell cycle or cell cycle non-specific, meaning they can work on any part of the cell cycle.4
An extravasation occurs when a chemotherapy drug accidentally leaks from the intended compartment (vein) into the surrounding tissue and beyond.1,5 Depending on the drug and action taken the leakage may result in injury; this may vary from a mild skin reaction to severe necrosis and possible amputation.5 Extravasations do not only occur when using a peripheral cannula but can occur when using any form of central venous access device (CVAD), for example, skin tunnelled central line, portacath or peripherally inserted central catheter (PICC).1,2,6,9
Types of extravasations
Chemotherapy drugs are classified according to their extravasation potential and professionals administering these drugs have a responsibility to understand the possible risk and manage it accordingly.2 There are various classifications of extravasation potential but largely they fit into three groups:
Non-vesicants – generally do not cause ulceration and rarely even produce an acute reaction as they generally do not impair or destroy tissue when extravasated.6 An example of a drug from this group is cyclophosphamide,5 a drug that is used in a number of regimens for a number of different cancers.
Irritants – have a tendency to cause pain at the cannula site and along the vein, they may cause an inflammatory reaction but rarely cause ulceration.2,7 An example from this group is 5-fluorouracil,5 again a widely used drug in everyday practice. A few irritants do have the potential to cause ulceration depending on the volume and concentration of the drug, for example, taxanes. 
Vesicants – have the potential to cause the most damage to a patient in terms of blistering and ulceration, which may lead to more serious damage, for example, tissue destruction and possible necrosis.1,2,5,6,9 Examples from this group would include anthracyclines (DNA binding) and vinca alkaloids (non-DNA binding).5 Due to the potential severity of a vesicant extravasation this is the one most feared by professionals. However, all extravasations should be feared and treated according to local guidelines based on best available evidence.2,5
Fig. 1: Partial Displacement Syndrome.
Risk factors
Individual patient risk factors include previous venous access and treatments, availability of the venous access and the quality.2,5,9 Veins that are small and fragile or hard and sclerosed, should be avoided. Other factors may include lymphoedema or lymph node dissection, obesity and other comorbidities such as diabetes, radiation damage, psoriasis and sensory deficit.1,2,5,9
The professional needs to consider the above factors along with the chemotherapy and supportive drugs to be administered, the duration and frequency of administration and choose the appropriate form of venous access device (VAD) for the individual patient.5,6,8 Discussion must take place with the patient regarding the risk of extravasation as a result of receiving intravenous chemotherapy, as despite the risk being small the potential of damage can be great.2,5,9
Prior to receiving the treatment, the professional would have explained the possible signs of an extravasation to look out for during the administration of the chemotherapy, which may include the following: pain, burning or stinging; redness and possible swelling around the cannula site; altered sensation, generally anything different.1,2,5,9
During the administration of the chemotherapy the professional may notice signs that should alert them to the fact that something is not right.9,10 These may include an increased resistance whilst administering the treatment if using a syringe or that the infusion becomes slow or sluggish, or infusion pump alarming. Another consideration should be if there is a lack or loss of blood return from the cannula.2,5,9
Consideration also needs to be given to what else could have happened as fortunately it will not always be an extravasation. The following possibilities should be considered – flare reaction, urticarial or hypersensitive reaction to the chemotherapy or supportive drugs or chemical phlebitis (Table 1).2,5,9
Why might they occur?
The occurrence of an extravasation is accidental and not necessarily the result of an error. One example of how an extravasation may occur is called ‘partial displacement syndrome’, which is where the cannula is partially in the vein and partially in the surrounding tissue (Figure 1).9 This would result in an increased flow rate and decreased resistance in the tissues, meaning an extravasation occurs without initial detection. 
Another example could relate to the type of VAD being used to administer the chemotherapy, especially when using a peripheral cannula. The cannula should be non-ported, which will minimise the risk of the cannula moving in the vein if the port was used for the administration of a drug. 
The requirement for and type of dressing used to secure the cannula, yet allow for constant observation; again to minimise any movement but also to minimise the risk of infection entering the blood supply.2 It could also occur due to a weakness in the wall of the vein due to previous cannulation or phlebotomy and you can never exclude the patient moving and dislodging the cannula, for example, when needing to go to the toilet.
What happens following an extravasation?
When an extravasation occurs the chemotherapy continues to damage the surrounding cells during the cell cycle. Initially the patient may experience pain and discomfort around the area, however the future progression of symptoms differs according to the extravasated drug.2,5 A vesicant drug has the potential to cause the most damage if not detected and managed in an appropriate and timely manner,9 however this should be the case for all possible extravasations.
Tissue damage can often develop slowly and may not necessarily be painful, with indurations and blistering not being visible immediately. However, it can then progress to ulceration and potential damage to nerves, tendons or ligaments depending on the area affected and may lead to the need for surgical intervention.2
Consequences of an extravasation
The incidence of extravasations is not as rare as professionals perceive and they account for between 0.1–7% of adverse events associated with receiving chemotherapy.2,6 Although this number may appear low it is still significant when considering the potential damage. Vesicant extravasations from a cannula is reported between 0.1–6% and from a CVAD is around 0.3–4.7%,11 the figure relating to cannula use is probably higher as most chemotherapy is administered in the ambulatory setting where cannulas are commonly used.
An extravasation would potentially impact on the patient life in other ways, not just from the initial damage to the skin, that is, psychologically and financially. It could affect their lifestyle, ability to work and their family’s, possibly interrupting their planned treatment regimen (Figure 2).2,9
Fig. 2: Possible patient consequences following an extravasation.
The impact an extravasation has on the professional involved in the delivery of the patient treatment must also be remembered;8 this could be a feeling of guilt and blame through to apprehension about administering chemotherapy in the future.1 There is also the possibility of a lawsuit against the organisation where the patient is receiving treatment.2
The European Oncology Nursing Society (EONS) developed a set of guidelines in the form of a toolkit in 2007,2 which have since been updated in 2012.5 The initial guidelines aimed to provide a greater understanding regarding extravasations from knowing what they are, how to minimise the risk of one occurring, recognising early signs of one, along with what else the symptoms may be. Importantly, the guidelines included easy to follow flowcharts for the use in clinical practice and also provided a greater appreciation of the consequences for the patient in terms of their quality of life and planned treatment. Other guidelines are included in the Multinational Association of Supportive Care in Cancer (MASCC) Textbook.6
Management options
There are a number of possible management options and the difficulty is to decide which is the most appropriate and when should it be implemented and by whom.2,5,6,9 Some of the options include the following:
Watch and wait – no direct intervention, usually consider for a small extravasation.5,6
Heat – used to disperse and dilute the extravasation, for example, vinca alkaloids and often used in combination with hyaluronidase.2
Cooling – used to constrict the blood supply and localise the extravasation.5,6,9
Dimethyl sulphoxide (DMSO) – is an oxygen free radical scavenger and although not licensed for the management of anthracycline extravasations is used ‘off license’ and has produced some good results.1,2,5,6,9 The data surrounding its use for this purpose is based on patient case studies and often relates to DMSO 99%. However, this strength is not always available and it is often the 50–55% that is used,1 which is intended for bladder instillation for the treatment of interstitial cystitis. Another key consideration is that DMSO can damage the ‘good’ skin around the extravasation if not applied correctly.
Hyaluronidase – used for the management of vinca alkaloid and taxane extravasations and is delivered via multiple subcutaneous injections around the extravasation site.5,6
Sodium thiosulfate – for the use of mechloretamine extravasations and again administered by injections given subcutaneously.5,6
Flush out technique – subcutaneous wash out involving injections of normal saline to the extravasation area.5,9 This must be performed by appropriately trained professionals and may require multiple treatments.2,9,10
Surgical intervention – wound cleaning and debridement to remove necrotic skin when an extravasation has not been managed appropriately or responded to chosen treatment, which may involve possible skin graft.5,6
Savene® – administered intravenously via a separate cannula sited away from the original extravasation for three days. The first infusion should be administered within six hours of the extravasation and the following infusions at 24 and 48 hours (±3 hours) following initial infusion.5,6 As Savene® is a chemotherapy drug, precautions will be needed when reconstituting and administering the treatments.12 Although Savene® is the only licensed antidote supported by clinical research and endorsed by many key organisations in their guidelines,5,6,12 it is not available in all hospitals administering chemotherapy.1,9
Need for documentation and audit of practice
The requirement concerning documentation does not only relate to when an extravasation has occurred but from when first meeting the patient, in terms of both verbal and written information provided, planned chemotherapy, venous access assessment and any individual concerns or considerations.1,2 Documentation is key to all aspects of patient care and a record of events that have occurred,2 and will demonstrate if local guidelines were adhered to.1,5
Practice needs to be continually audited in terms of changes in available evidence influencing practice,2 patient outcomes and any trends in incidents occurring as a result of chemotherapy delivery. This is a key requirement in practice as the current published evidence is becoming rather dated and difficult to relate to current practice, that is, the incidence of the occurrence of extravasations in today’s practice will be different to that of five or ten years ago due to the skills of professionals administering the chemotherapy and the ongoing monitoring patients receive. Up to date evidence is required to ensure patients receive the highest standard of evidence-based care to minimise unnecessary complications.
The future
There is still a great deal of work needed to ensure the patient receives the appropriate management should an extravasation occur due to the limited evidence. It is generally considered that the occurrence of extravasations has reduced due to the training of professionals and administration technique when administering chemotherapy,5,9 yet the incidence of extravasations is still perceived as under-reported.1
There is a need to collate data regarding the incidence and management strategies implemented, along with patient outcomes in terms of damage caused and clinical outcomes.9 This data could them be used to develop national recommendations regarding which management option to implement and when.
There is and will always remain a need for practice guidelines to be based on the best available evidence and a need for ongoing professional education and assessment of competencies in both delivery of chemotherapy and management of potential side effects.2,3,5,9