Extravasation is always a risk when administering medicines intravenously. This is when the infused drug infiltrates the tissue surrounding the injection site. The resulting injury can range from mild to lifethreatening, depending on whether the drug involved is classified as an irritant or a vesicant.
The Infusion Nurses Society (INS) defines a vesicant as “an agent capable of causing injury when it escapes from the intended vascular pathway into the surrounding tissue.”1
Anthracyclines are vesicants commonly used to treat cancer. More than 500,000 doses of anthracyclines are administered intravenously in the United States each year,2 and an estimated 0.1% to 1.0% of doses involve extravasation.3 Although extravasation is rare, it is not always preventable. This is partly because many patients with cancer have thin, fragile, mobile veins, and multiple punctures are required to administer intravenous (IV) chemotherapy.4 The literature also documents unexpected extravasations via central venous catheters.5-8
Anthracycline extravasation requires immediate attention to mitigate the risk of severe—even permanently disabling—tissue damage.9 The potential consequences underscore the need for nurses to know and adhere to national evidence-based practice guidelines for managing anthracycline extravasation. They should also use this knowledge to make the case to their employer for following best practices.
How Anthracycline Extravasation Affects Patients Symptoms of anthracycline extravasation can be immediate or delayed and typically include swelling; redness; and pain, itchiness, or burning at the site of infusion.9 As damage progresses, skin discoloration, induration, and blistering are often observed.
Sequelae of a minor extravasation sometimes heal without involved care. More extensive cases of extravasation can progress to ulcers, tissue necrosis, and infection. These patients might require plastic surgery, skin grafting, physical therapy, and other interventions over several months that leave them scarred or disfigured. In extreme cases, they might be left with permanent physical impairment, such as nerve damage, partial loss of hand function, or amputation.10
Extravasation sometimes leads to treatment delays, particularly for patients who develop ulcers. Because chemotherapy has a negative effect on fast-growing cells like those involved in healing, it might need to be withheld until the ulcer resolves, even if surgical treatment is not required. Treatment interruptions can reduce the overall effectiveness of anticancer therapy and contribute to poorer outcomes.9
Treatment Guidelines Improve Care The INS and the Oncology Nursing Society (ONS) have issued guidelines on chemotherapy administration that address treatment extravasation.1,11 Both sets of guidelines specify dexrazoxane for injection (Totect) as the only medical treatment approved by the US Food and Drug Administration to manage anthracycline extravasation.1,11 TopoTarget USA, which manufactures dexrazoxane, packages the antidote as part of a single- patient emergency treatment kit containing 10 vials of dexrazoxane and 10 vials of diluent.12
If there are symptoms or other signs of anthracycline extravasation (such as fluid leaking from the injection site or problems with the rate of infusion), guidelines call for stopping treatment, assessing the site, and cooling it with an ice pack for 15 to 20 minutes.1,11 The ice needs to be removed from the site for at least 15 minutes before administering dexrazoxane, which INS guidelines say should be initiated within 6 hours of extravasation.1 The drug is infused into a large vein in the unaffected arm.
The guidelines cite evidence from 2 prospective multicenter studies in support of the dexrazoxane recommendation. The studies showed that dexrazoxane prevented tissue necrosis requiring surgical treatment in 98% of patients (Figure).13 The remaining 2% reflects the experience of 1 study participant who had experienced massive anthracycline extravasation, encompassing an area 253 cm2.13 Additionally, 74% of patients treated with dexrazoxane experienced no delay in chemotherapy.13
National treatment guidelines reflect the best practices according to evidence in the medical literature and outcomes observed in hospitals and in the community. They are useful tools that aid in decision making on effective care and promote patient safety.
Guidelines also provide peace of mind for the nursing professional. In addition to caring for the patient at the bedside and responding to the patient’s needs, nurses usually bear the hefty responsibility of placing an IV line or catheter, each time putting their career, license, and heart on the line.
When extravasation occurs, a nurse’s first impulse is to assume blame. Even if the pharmacy failed to place the antidote on the formulary or did not release an adequate supply of antidote, the nurse might still feel responsible. I continue to be haunted by a case of anthracycline extravasation that occurred in the late 1980s, before an antidote existed. The patient had a large doxorubicin extravasation through a vein in the upper arm that progressed to severe tissue necrosis and infection. Eventually, the patient’s arm was amputated.
Fortunately, with national guidelines now in place on the proper placement of IV catheters and patency assessment during an infusion of vesicant therapy, extravasations are few and far between. When they do occur, the availability of an antidote and guidelines on its administration make severe extravasationrelated complications such as amputations far less likely.
Spending Money to Save Money Although evidence-based medicine has gained widespread acceptance in medical and nursing circles, the call is growing for all clinicians and hospitals to adhere to national treatment guidelines. With Donald Berwick as the new administrator of the Centers for Medicare & Medicaid Services (CMS), there will likely be even more emphasis on patient-centered, evidence-based approaches to care. Berwick is the former president and chief executive officer of the Institute for Healthcare Improvement, a nonprofit organization that worked to advance evidence-based medicine throughout the world. Berwick is expected to base CMS reimbursement and policy decisions partly on national treatment guidelines; private insurers are expected to follow the agency’s lead. At some point, reimbursement for treating complications like extravasation might depend on being able to show evidence of adherence to national guidelines.
Although hospitals are loath to admit it, economic considerations have the potential to influence their degree of adherence to national guidelines. The current economy has led hospitals to become increasingly cost conscious and sometimes tempts even those committed to evidence-based practice to replace a more expensive proven treatment specified by the guidelines with a less expensive unproven alternative.
In the case of dexrazoxane for injection, some hospitals are pooling their resources to reduce their costs. Each emergency kit contains enough dexrazoxane to satisfy the full 3-day regimen required to treat anthracycline extravasation. 12 Three hospitals, for example, will share the expense of a single kit, dividing the doses so that each hospital has a 1-day supply. Such resource sharing is potentially problematic, eroding a hospital’s control over supplies. What if a hospital is unwilling to hand over its suphour window for initiating dexrazoxane after suspected anthracycline extravasation? What if a second patient needs the antidote before the supply is restocked? Another concern is that one hospital might be less diligent than another in monitoring product expirations.
Hospitals need to recognize that not having dexrazoxane readily available to treat a case of anthracycline extravasation will potentially be more costly for the hospital, particularly if a patient develops necrosis and infections. Insurers might also balk at paying to treat conditions that adherence to guidelines would likely have prevented.
Best Practices: In Everyone’s Best Interest Nurses are often directly involved when anthracycline extravasation occurs, underscoring their important role in patient care. Evidence-based treatment guidelines are clear in recommending prompt administration of dexrazoxane for injection as an antidote to anthracycline extravasation; failure to adhere to these guidelines puts patients at risk of significant morbidity.
A nurse who is aware of the availability of an antidote to complications associated with a specific caustic agent but fails to use it is open to potential legal liability as a named defendant in a malpractice lawsuit. Lack of control over supplies or pharmacy cost-cutting does not alleviate a nurse of this responsibility. A hospital administration that is familiar with the ONS and/or INS guidelines but does not make the antidote available faces similar liability risks.
Nurses must therefore be more outspoken when it comes to advocating for best practices. This requires staying informed of available resources, which goes beyond specific medications to include individuals within the system who can offer support and cooperation. Pharmacists typically hold the purse strings on pharmaceuticals in hospital systems. On cologists might be supportive of nurses’ requests but ultimately defer to the pharmacists. This makes it even more important for nurses to speak up and outline the case for adhering to best practices on anthracycline extravasation. Begin by citing the emphasis of the national guidelines on timely and appropriate intervention as a means of providing quick resolution and preventing costly, debilitating complications.
References
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