Practice Issues J Oncol Pharm Practice 2018, Vol. 24(2) 129–138 ! The Author(s) 2017 Pharmacological management Reprints and permissions: sagepub.co.uk/journalsPermissions.nav of anticancer agent extravasation: DOI: 10.1177/1078155217690924 A single institutional guideline journals.sagepub.com/home/opp Jaime Kimmel1, Patrick Fleming2, Sandra Cuellar2, Jennifer Anderson3 and Christina Mactal Haaf2 Abstract Although the risk of extravasation of a chemotherapy (anticancer) medication is low, the complications associated with these events can have a significant impact on morbidity and health care costs. Institutions that administer anticancer agents should ideally have a current guideline on the proper management of the inadvertent administration of these toxic medications into tissues surrounding blood vessels. It is imperative that the health care team involved in administering drugs used to treat cancer be educated on the risk factors, preventative strategies and treatment of anticancer extrava- sations, as well as practice safe and proper administration techniques. Anticancer agents are generally divided into classes based on their ability to cause tissue damage. The review of current published guidelines and available literature reveals a lack of consensus on how these medications should be classified. In addition, many recently approved drugs for the treatment of cancer may lack data to support their classification and management of extravasation events. The treatment of the majority of extravasations of anticancer agents involves nonpharmacological measures, potentially in the ambu- latory care setting. Antidotes are available for the extravasation of a minority of vesicant agents in order to mitigate tissue damage. Due to the limited data and lack of consensus in published guidelines, a working group was established to put forth an institutional guideline on the management of anticancer extravasations. Keywords Antineoplastic, anticancer, chemotherapy, extravasation, irritant, vesicant Date received: 8 September 2016; revised: 13 December 2016; accepted: 26 December 2016 Introduction include persistent pain, burning, stinging, swelling and Anticancer agents, which are commonly administered either blanching or erythema at the site of injection or via the intravenous (IV) route, are generally separated along the course of a vein. Unlike irritants, vesicant into two broad categories based on their ability to cause medications notably are capable of causing blistering, tissue injury: vesicants or irritants. Vesicants are defined ulceration and tissue necrosis if administered outside of as agents that are capable of causing soft tissue damage a vein. Such a clinical scenario may lead to death if left by causing blistering and necrosis, while irritants cause 1 inflammatory reactions. Additionally, the European 1Department of Pharmacy, University of Texas MD Anderson Cancer Oncology Nursing Society (EONS) describes a third cat- Center, USA egory of intravenous medications, the nonvesicants.2 2Department of Pharmacy, University of Illinois Hospital & Health Sciences System, USA Nonvesicants are agents that do not produce necrosis 3 or inflammation.3 Extravasation is the inadvertent Department of Pharmacy, University of Chicago, USA administration of a vesicant solution from a vein, Corresponding author: Christina Mactal Haaf, Department of Pharmacy, University of Illinois while infiltration refers to leakage of an irritant into 1,2,4 Hospital & Health Sciences System, 833 S Wood St, Rm 164, Chicago, IL the extravascular space. Initial symptoms of 60612, USA. extravasation and infiltration are clinically similar and Email: [email protected] 130 Journal of Oncology Pharmacy Practice 24(2) untreated and, therefore, may necessitate surgical recognize and manage extravasation injuries to ensure debridement or skin grafting, possibly resulting in a safe level of care for individuals receiving these permanent patient disability and disfigurement.4 agents. Prevention is the ideal approach when poten- Extravasation of an anticancer agent is potentially a tially encountering anticancer extravasation injury. medical emergency that requires prompt recognition Strategies to prevent or minimize antineoplastic medi- and action to ensure patient safety. The term ‘‘antic- cation extravasation are listed in Table 1. ancer agents’’ in this article describes classic cytotoxic chemotherapy agents as well as biotherapy. Although the exact incidence is unknown due to the Management lack of a central reporting database, it is estimated that Anticancer drug classification extravasation occurs at 0.1–6% for all cytotoxic drug administrations.1,5,6 Some data suggest that the overall Multiple organizations, including the European Society incidence is decreasing due to better recognition and of Medical Oncology-European Oncology Nursing training in management techniques.2 In addition, the Society (ESMO-EONS) and the Oncology Nursing routine use of central venous administration could Society (ONS), have guidelines for management of also contribute to the decreased incidence as central chemotherapy extravasations.2,5 However, there is a venous access devices (CVAD) are associated with lack of consensus on the classification of intravenously decreased risk of extravasation. administered anticancer drugs and their proper extravasation management. In an effort to construct Risk factors and prevention an institutional guideline, a working group at the University of Illinois Hospital and Health Sciences There are a variety of risk factors associated with System (UIHHS) was organized to review the current extravasation that can be separated into those asso- literature in order to classify and recommend optimal ciated with the clinician, patient, agent, and device pharmacological extravasation strategies for select (Table 1). Identification of potential risk factors prior anticancer intravenous agents. to intravenous anticancer medication infusions will A review of the literature incorporating manufac- mitigate inadvertent administration of these medica- turer package inserts, oncology nursing society guide- tions into the extravascular space. In addition, oncol- lines and available patient case reports demonstrated ogy nurses should receive specialized education and wide variability distinguishing several intravenous training in order to appropriately administer chemo- anticancer medications based on tissue damage poten- therapy and biotherapy, as well as to promptly tial. Our PubMed and Google Scholar search terms Table 1. Extravasation risk factors and prevention.2,5–8 Risk factors Prevention strategies Clinician related Cannulation technique – untrained or Educate all staff administering chemotherapies on risk inexperienced staff, multiple attempts at identification, extravasation prevention and management, cannulation appropriate use of venous devices, and proper documentation Patient related Age: >60 or 10 Educate patients on risk of extravasation and instruct Fragile veins them to report any pain, burning, or change in sensation Compromised circulation at injection site Severe peripheral vascular disease, lymphe- Instruct patient not to reposition or remove cannula dema, superior vena cava syndrome, advanced diabetes, Raynaud syndrome Agent related pH <5or>9 Preferred route of administration is via central IV access High osmolality Vesicant infusions lasting <60 min may be administered Cytotoxicity–DNA binding more likely than peripherally if observed during the entire infusion with IV non-DNA binding patency confirmed every 5–10 min Device related Metal needles Use plastic cannulas Large gage catheter (<18 gage) Use smallest gage feasible, 18 to 20 gage is preferred Inadequately secured catheter Stabilize and secure needle with transparent dressing Location: dorsum of hand or wrist, antecubital Location: place cannula in forearm fossa Kimmel et al. 131 included: extravasation, management, injury, chemo- antibody–drug conjugates is listed in ONS or EONS therapy, antineoplastic, cytotoxic, and individual drug guidelines. and antidote names combined with Boolean operators. Additionally, with the exception of ixabepilone, the Papers describing surgical management of extravasa- newer antimicrotubule agents, eribulin and cabazitaxel, tion were excluded. In order to establish a classification are not included in either nursing guidelines and lack scheme for our institution, we first examined how major published evidence to accurately support classification. nursing organizations describe the extravasation poten- Eribulin and ixabepilone were classified as irritants that tial of commonly used anticancer agents. A summary of may have vesicant like properties as they are mechan- these anticancer drug classifications as either vesicants istically similar to the taxanes and vinca alkaloids. The or irritants is compiled in Table 2. If guidance from package insert for cabazitaxel does not identify this ONS and EONS was conflicting, our working group medication as an irritant or vesicant.9 However, due made a conservative recommendation. Additionally, to the structural and mechanistic similarity to doce- anticancer agents were initially limited to one of two taxel, the working group classified cabazitaxel as a categories, vesicants or irritants, as nonpharmacologi- vesicant. cal management suggestions for ‘‘nonvesicant’’ extrava- sation were identical to those for irritants. In situations General treatment measures where EONS listed a medication as a nonvesicant,