The September/October 2024 edition of the Journal of Infusion Nursing shared the long-awaited updated list of non-antineoplastic vesicants and a companion literature review regarding the midline catheter.1 In addition, Barb Nickel presented a webinar on extravasation treatment on 9/18/24.2 The webinar was recorded and is now available in the INS Learning Center. These resources support the 2024 INS Infusion Therapy Standards of Practice and highlight extravasation preventative measures, vesicant characteristics, and strategies for early recognition to mitigate patient harm.3 Clinicians are encouraged to use these resources to enhance the extravasation prevention and management strategies at their organizations.
Table 1.
Important Definitions
| Term | Definition |
| Vesicant | An agent capable of causing tissue damage when it escapes from the intended vascular pathway into surrounding tissue |
| Irritant | An agent capable of producing discomfort or pain as a result of irritation in the internal lumen of the vein with or without immediate external signs of vein inflammation |
| Extravasation | Inadvertent infiltration of vesicant solution or medication into surrounding tissue |
| Infiltration | Inadvertent administration of a nonvesicant solution or medication into surrounding tissue3 |
In 2017, a document titled, “Development of an Evidence-Based List of Noncytotoxic Vesicant Medications and Solutions,” by Gorski et al,4 established an initial list of non-cytotoxic vesicants to fill a critical gap and to bring a level of standardization in this area of practice. In Fall of 2021, a new task force, led again by Lisa Gorski, was formed to revise this important work with an in-depth review of current evidence. After 2 years of exhaustive review and revision, “Development of an Evidence-Based List of Non-Antineoplastic Vesicants” became a reality. Members of this task force included Lisa Gorski, MS, RN, HHCNS-BC, CRNI®, FAAN; Jennie Ong, PharmD; Ruth Van Gerpen, MS, RN, APRN-CNS, AOCNS, BC-PMGT; Barb Nickel, APRN-CNS, CCRN, CRNI®; Kathy Kototis, RN, BS, MBA; and Lynn Hadaway, Med, RN, CRNI®.1
Two important early decisions by the task force differentiate this 2024 version from the initial 2017 vesicant list. The key word in the title is the use of “non-antineoplastic” to identify that this list addresses vesicants used in clinical settings outside of oncology. The 2017 document used the term noncytotoxic since, at that time, cytotoxic was the term more commonly used to refer to oncology-related medications. In the ensuing years, however, the cytotoxic nature of medications used in many clinical settings, such as vancomycin, has gained clarity. The term non-antineoplastic was chosen by the task force as a more accurate term for this list of vesicants.
The second task force decision was to more clearly delineate the risk rating of the vesicant classes. The 2017 document listed vesicants as red and yellow based on the earlier work of Clark et al.4 As the 2024 task force began to compile the revised evidence table of vesicants, they determined that the risk categories should be more clearly labeled as high, moderate, and cautionary. In addition, they differentiated risk based on 3 main factors: published or documented cases of patient harm, existence of a mechanism of extravasation injury, and drug prescribing information. To place a vesicant in the high-risk category with a potential to cause significant injury, at least 2 cases of published cases with permanent functional impairment were required. Moderate risk was indicated with documented cases of injury or drug prescription documentation of extravasation injury, including up to 1 case of permanent function impairment. Cases with a valid proposed mechanism of injury from the medication were given specific attention as defined in the document (Table 1).4(p293) The cautionary label included those medications with a single case of reported injury, a known mechanism of injury, or unclear causation.
Multiple sources were reviewed to compile the final vesicant evidence table, including case reports/studies, systematic reviews, narrative reviews, FDA FAERS report, Trissel’s Clinical Pharmaceuticals, Lexicomp, and Micromedex. Medications were screened for inclusion if they were excluded from the 2017 list for insufficient evidence; listed as a vesicant in literature published after 2017; or listed in an IV drug reference with reference to extravasation. The high and moderate risk table includes the following categories of medications: antimicrobials, electrolytes/nutrition, cardiovascular, sedatives/antiepileptics, and an “other” category. Included with each vesicant is a description of the supporting evidence for its risk classification and the associated mechanism(s) of injury.
The task force built upon the important work by Ong and Van Gerpen5 in their 2020 JIN article titled “Recommendations for management of non-cytotoxic vesicant extravasations.” Concise descriptions of mechanisms of injury are included in the article to enhance the clinician’s ability to mitigate the risk of harm from these medications. Five main mechanisms for injury are described: nonphysiologic pH (high risk <4.0 or >9.0; moderate risk 4.0 – 5.0 or 7.5 – 9.0); vasoconstriction, osmolarity, cytotoxicity, and absorption refractory (vesicants with insolubilities or limited reabsorption). Each of these mechanisms can cause damage, even necrosis, when they escape from the venous pathway into surrounding tissues. The extent of the damage is dependent on many factors, including amount and concentration of the vesicant(s) that has extravasated, the length of time that the tissue has been exposed to the vesicant(s), the patient’s current status, and the location of the extravasation.1,5-8
Extravasation prevention is the most important strategy in this toolbelt. Several resources are now available to optimize patient outcomes. Within the non-antineoplastic document, the task force has included discussion of the specific risks of antimicrobials, electrolytes/nutrition, sedatives/antiepileptics, contrast media, radiopharmaceuticals, monoclonal antibodies, and cardiovascular medications. Within the cardiovascular category, peripheral administration of vasopressors has been the subject of extensive research and a recent practice shift to provide prompt treatment and to reduce central vascular access device (CVAD) utilization. The 2024 task force has provided an evidence table reviewing the current evidence on peripheral vasopressor administration and a discussion of strategies to safely deliver vasopressors via the peripheral route for the initial 24-hour period.1(p308-313)
A very important resource developed by the 2024 task force is the Extravasation Prevention Checklist, now available on the INS Learning Center. The checklist, located in the Appendix, draws from multiple references, including the INS Standard 44, “Infiltration and Extravasation” and identifies strategies in extravasation prevention, recognition, and management.1,3(p338-346) This article includes important recommendations for health care organizations, including standardization of their vesicant list and creating readily accessible resources to guide safe vesicant administration. A foundational prevention strategy is intentional vascular access device (VAD) selection that adheres to principles of vascular health and preservation, placing the correct VAD for the patient’s current needs with daily review to ensure optimal management. An important table identifies risk factors to be used to develop patient-specific interventions. It outlines VAD-specific risks that should be used to optimize vessel health and preservation through proper VAD selection, placement, and management. This checklist then applies this information to identify strategies to safely administer vesicants via peripheral versus centrally placed VADs. Finally, the checklist outlines specific steps recommended for extravasation management.3(p321)
Another crucial extravasation prevention strategy is the regular assessment and maintenance of VAD patency. INS Standard 46, “VAD Occlusion,” includes the universal Standards statement: “46.1 Vascular access device (VAD) patency is routinely assessed and defined by the ability to flush all catheter lumens without resistance after establishing blood return from each lumen.” This is especially important with the recent increase in peripheral administration of vesicants to reduce CVAD utilization. Unfortunately, loss of blood return and occlusion are frequently reported complications with all peripheral catheters. That same standard recommends that when blood return is sluggish/absent in a peripheral VAD intended to be used for vesicant administration, a transition to a more appropriate VAD should be accomplished as soon as clinically possible. Occlusion, whether mechanical or thrombotic in nature, can increase intraluminal pressure, potentially causing inadvertent delivery of a vesicant into surrounding tissue.3
Taskforce discussions regarding increased peripheral VAD extravasation risks prompted concerns regarding the recent increased utilization of the midline peripheral catheter for vesicant administration. These concerns resulted in a companion article in the September/October ’24 JIN issue, an extensive review by Hadaway and Gorski,9 “Infiltration and Extravasation Risk with Midline Catheters: A Narrative Literature Review.” It includes delineation of midline catheter definitions, vein anatomic measurements, case reports of midline infiltration/extravasation, and midline tip locations.
In the aforementioned September 2024 INS Webinar, “Extravasation: Exploring Treatment Options in a Case Study Approach,” Barb Nickel utilized her work on the task force, authorship of the “Infiltration and Extravasation” Standard, and multiple case studies to present a verbal review of extravasation prevention and management. The webinar includes a clear and convincing review of extravasation-related patient harm through a review of treatment options, including cold/warm packs, hyaluronidase, sodium thiosulfate, dexrazoxane, phentolamine, saline washout, dressing options, and surgical treatment. Specific case studies apply these options in the treatment of a variety of extravasation injuries from doxorubicin, norepinephrine, parenteral nutrition, amiodarone, vancomycin, and calcium gluconate.2
Extravasation injuries represent significant patient harm and require a focused effort by health care organizations and clinicians to improve outcomes. This includes standardization of the organization’s vesicant list to ensure that clinicians provide patient-centered VAD insertion, selection, and management to prevent extravasation injuries. The resources reviewed above are excellent evidence-based tools to build/revise clinician education and competency evaluation, to design process improvements, and to optimize patient outcomes with vesicant administration.
REFERENCES
- Gorski L, Ong J, Nickel B, Van Gerpen R, Kokotis K, Hadaway L. Development of an evidence-based list of non-antineoplastic vesicants: 2024 update. J Infus Nurs. 2024;47(5):290-323. doi:10.1097/NAN.0000000000000568
- Nickel, B. INS Webinar presented on 9/18/24. “Extravasation: Exploring Treatment Options in a Case Study Approach.”
- Nickel B, Gorski LA, Kleidon TM, et al. Infusion therapy standards of practice, 9th ed. J Infus Nurs. 2024;47(1S Suppl 1):S1-S285. doi:10.1097/NAN.0000000000000532
- Gorski LA, Stranz M, Cook LS, et al. Development of an evidence-based list of noncytotoxic vesicant medications and solutions. J Infus Nurs. 2017;40(1):26-40. doi:10.1097/NAN.0000000000000202
- Ong J, Van Gerpen R. Recommendations for management of non-cytotoxic vesicant extravasations. J Infus Nurs. 2020;43(6):319-343. doi:10.1097/NAN.0000000000000392
- Manrique-Rodríguez S, Heras-Hidalgo I, Pernia-López MS, et al. Standardization and chemical characterization of intravenous therapy in adult patients: a step further in medication safety. Drugs R D. 2021;21(1):39-64. doi:10.1007/s40268-020-00329-w
- Poderós TG, Cabero JJF, Domínguez MV. Classification of non-anti-neoplastic intravenously administered drugs according to their toxicity risk: the path towards safe drug administration. Eur J Hosp Pharm. 2024;31(2):107-110. doi:10.1136/ejhpharm-2022-003294
- Shibata Y, Taogoshi T, Matsuo H. Extravasation of noncytotoxic agents: skin injury and risk classification. Biol Pharm Bull. 2023;46(6):746-755. doi:10.1248/bpb.b22-00850
- Hadaway L, Gorski LA. Infiltration and extravasation risk with midline catheters: a narrative literature review. J Infus Nurs. 2024;47(5):324-346. doi:10.1097/NAN.0000000000000566
