Infiltration or Extravasation of Oxaliplatin

Quick Facts

• Oxaliplatin may be listed as an irritant or as a vesicant
• Knowing the risks of extravasation and following your institution’s policy are ways to prevent this emergency
• When possible, oxaliplatin should be administered through a central venous access device  

Background

Extravasation is defined as the inadvertent leakage of a nonvesicant solution into surrounding tissues, and extravasation is defined as the inadvertent leakage of a vesicant solution  into surrounding tissues.1  Cancer patients are at risk for extravasation, because their veins may be fragile from previous chemotherapy or radiation, poor nutrition, and multiple venipunctures.^1,2

Agents and Reactions

• Vesicants cause blistering, tissue damage, or tissue necrosis referred to as chemical cellulitis.^1-3 Examples include alkylating agents (cisplatin), antitumor antibiotics (doxorubicin, mitomycin, epirubicin), vinca alkaloids (vincristine, vinorelbine), and taxanes (paclitaxel).^1-3
• Irritants cause short-lived burning, with or without inflammation and pain, but not tissue necrosis. Examples are alkylating agents (carboplatin, ifosfamide, oxaliplatin) and liposomal doxorubicin.1-3

Oxaliplatin, an agent commonly used to treat CRC, has been described as both a vesicant and irritant.4-9 Although tissue damage does not appear to be as severe as with other known vesicants, most published case reports describe progressive local tissue necrosis, induration, edema and hyperpigmentation. 4-9 Kretzschmar and colleagues4 retrospectively reviewed 11 cases of oxaliplatin extravasation and concluded that even with large volume (>40mg) extravasations of oxaliplatin, there was no evidence of tissue necrosis and the long-term outcomes were good. The authors also concluded that extravasation of oxaliplatin did not compare with that of the typical vesicants such as anthracyclines.

Foo and colleagues⁵ documented a case of peripheral oxaliplatin extravasation in which the patient developed erythema that formed a peau d’orange appearance. It progressed to form a red-brown and tender induration, which persisted over the next month. The patient developed paresthesias and had persistent skin fibrosis and numbness at the area of the extravasation. The authors concluded that oxaliplatin should be considered a vesicant.

Sorich and colleagues9 recommend regarding oxaliplatin as a vesicant in practice and suggest that oxaliplatin may not be an appropriate agent for peripheral administration. Kennedy et al5 reported significant muscle necrosis and fibrosis following antecubital extravasation of oxaliplatin and suggest that oxaliplatin may not be an appropriate agent for peripheral administration. The mechanism of action of oxaliplatin – binding to nucleic acid for a prolonged period – may be responsible for slow development of sequelae, lack of spontaneous resolution and may increase the potential of long-term extravasation injury.6-8 

Pericay et al10 reported that fewer than 10 cases of oxaliplatin extravasation through a central venous access had been described to date. They describe a case report of a 165mg dose of oxaliplatin that extravasated through a central venous access and concluded that the effect was that of an irritant rather than a vesicant. Full recovery from toxicity was achieved.

Preventing Extravasation

In most instances, extravasation can be prevented by monitoring the administration site during continuous IV chemotherapy. Nurses who administer IV chemotherapy should complete a certified chemotherapy course and demonstrate essential clinical skills. ONS Chemotherapy and Biotherapy Guidelines and Recommendations for Practice3 is the reference text for ONS chemotherapy certification, and provides evidence-based guidelines. Care should always be used when administering chemotherapy through a peripheral IV site. Peripheral IVs should be located in areas of good circulation and avoid the antecubital space. Whenever possible, oxaliplatin should be administered through central venous access, preferably placed prior to the first oxaliplatin infusion.⁸ 

The Joint Commission11 and the U.S. Department of Health and Human Services, Agency for Health Care Research and Quality12 have stated that the single most important way to prevent errors is for patients to be active members of the healthcare team. For patients receiving IV chemotherapy, playing an active role in promoting safety can help prevent chemotherapy extravasation. Information to teach patients to prevent harm from extravasation includes: (a) the risk of extravasation, (b) signs and symptoms to report, (c) interventions to prevent dislodgement of IV access, and (d) the availability of central venous access devices if peripheral access is poor. 13 A patient safety article by Smith14 provides samples of two patient education handouts to increase patient awareness of their role in preventing extravasation. 

Figures 1, 2.

Foo et al, used with permission.

Management of Oxaliplatin Extravasation 

Current guidelines recommend the following steps at the first sign of infiltration or extravasation:

• Stop administration of IV fluids immediately
• Disconnect the IV tubing from the device
  
• Attempt aspiration of the residual drug from the IV device
  
• Notify the physician or advanced practice nurse.15

Nursing interventions for the optimal management of oxaliplatin extravasation remain uncertain.8 Prescribing information for oxaliplatin (Eloxatin, sanofi-aventis, Bridgewater, NJ) contains no specific recommendations for management of extravasation.16 Management of oxaliplatin extravasation should include warm compresses, because cold may aggravate neuropathy5,8 although no randomized clinical data exist to support this practice. Sodium thiosulfate 0.16 Molar (mole/liter) injected subcutaneously into the extravasation site has been reported as effective in case reports of oxaliplatin extravasation.5,7 Sodium thiosulfate 0.16 M solution is prepared by mixing 4 mL sodium thiosulfate 10% solution with 6 mL sterile water for injection. The solution (5mL) is injected subcutaneously into the extravasation site.17 The use of sodium thiosulfate for oxaliplatin extravasation has not been confirmed through clinical trials. Oral dexamethasone for 10-14 days after oxaliplatin extravasation may reduce inflammation.3,4,9 Serial photography is useful to supplement carefully written documentation of the extravasation and resulting wound bed.18 Documentation of events prior to, during and following extravasation management must be documented in the patient medical record. Documentation should include grading the extravasation according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Effects (CTCAE) (currently v 4.02).19 

The extent of injury depends on the agent, dose, concentration, and volume. It is advisable to administer vesicants through a central line.3 Extravasation via a central line is most commonly caused by a dislodged needle in the port. Oncology nurses should follow their institution’s protocol for assessment of central venous access if the extravasation occurred while using a central venous access device. 

Assessment Tools

National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.02_2009-09-15_QuickReference_8.5x11.pdf  (General disorders and administration site conditions, pages 22-23)

Resources 

Additional information on extravasation can be found in the following articles:

• Sauerland C, Engelking C, Wickham R, Corbi D. Vesicant extravasation part I: Mechanisms, pathogenesis, and nursing care to reduce risk. Oncol Nurs Forum. 2006;33:1134-1141.
• Wickham R, Engelking C, Sauerland C, Corbi D. Vesicant extravasation part II: Evidence-based management and continuing controversies. Oncol Nurs Forum. 2006;33:1143:1150. 
• Carroll-Johnson RM. (Ed.) Letters to the Editor. Oncol Nurs Forum. 2007;34:275-280. (Letters in reply to Sauerland et al & Wickham et al articles above.)

 References

1. Infusion Nurses Society. Infusion nursing standards of practice. J Infus Nurs. 2006;29(1)(suppl):S1-S92.
2. Apisarnthanarax N, Duvic MM. Dermatologic complications of cancer chemotherapy. In: Kufe DW, Pollock RE, Weichselbaum RR, et al, eds. Cancer Medicine 6. Vol. 2. Hamilton, Ont: BC Decker; 2003: 2469-2476.
3. Polovich M, Whitford JM, Olsen M, eds. Chemotherapy and Biotherapy Guidelines and Recommendations for Practice. 3rd ed. Pittsburgh, Pa: Oncology Nursing Society; 2009: 105-111.
4. Kretzschmar A, Pink D, Thuss-Patience P, et al. Extravasation of oxaliplatin. J Clin Oncol. 2003;21:4066-4069.
5. Foo KF, Michael M, Toner G, et al. A case report of oxaliplatin extravasation. Ann Oncol. 2003;14:961-962.
6. Kennedy JG, Donahue JP, Hoang B, et al. Vesicant characteristics of oxaliplatin following antecubital extravasation. Clin Oncol (R Coll Radiol). 2003;15:237-239.
7. Baur M., Kienzer HR, Rath T, Sittrich C. Extravasation of oxaliplatin – Clinical course. Onkologie. 2000;23:468-471.
8. de Lemos ML, Walisser S. Management of extravasation of oxaliplatin. J Oncol Pharm Pract. 2005;11:159-162.
9. Sorich J, Taubes B, Wagner A, Hochster H. Oxaliplatin: Practical guidelines for administration. Clin J Oncol Nurs. 2004;8:251-256.
10. Pericay C, López A, Soler JR, Bonfill T, Dotor E, Saigí E. Extravasation of oxaliplatin: an infrequent and irritant toxicity, Clin Transl Oncol. 2009; 11:114-116.
11. Joint Commission. Standards improvement initiative: Goal 13. Available at http://www.jcrinc.com/2009-NPSGs-Goal-13/  Accessed February 23, 2010.
12. U.S. Department of Health and Human Ser¬vices, Agency for Health Care Research and Quality. 20 tips to help pre¬vent medical errors. Patient fact sheet. Available at http://www.ahrq.gov/consumer/20tips.htm  accessed February 18, 2010.
13. Schulmeister L. Managing vesicant extravasation. Oncologist. 2008;13:284-288.
14. Smith LH. National patient safety goal #13: Patients’ active involvement in their own care: Preventing chemotherapy extravasation. Clin J Oncol Nurs. 2009;13:233-234.
15. Doellman D, Hadaway L, Bowe-Geddes LA, et al. Infiltration and extravasation: Update on prevention and management.  J Infus Nurs. 2009;32:203-211.
16. sanofi-aventis. Eloxatin prescribing information, 2009. Available at http://products.sanofi-aventis.us/eloxatin/eloxatin.pdf  Accessed February 18, 2010.
17. University of Illinois at Chicago, College of Pharmacy Drug Information Group. Drug Extravasation: Management summary and update. Retrieved on February 18, 2010 from http://www.uic.edu/pharmacy/centers/drug_information_center/faq/extravasation.php
18. Froiland K. Extravasation injuries: Implications for wound, ostomy and continence nursing. J Wound Ostomy Continence Nurs. 2007;3:299-302.
19. National Cancer Institute (NCI). Common Terminology Criteria for Adverse Effects (CTCAE), v 4.02. Available athttp://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.02_2009-09-15_QuickReference_8.5x11.pdf (General disorders and administration site conditions, page 22-23)

Key Definitions

antecubital space—the region of the arm in front of the elbow
induration—localized hardening of soft tissue of the body 
peau d’orange—a dimpling of the skin that gives it the appearance of the skin of an orange
tissue necrosis—death of cells or tissues through injury or disease, especially in a localized area of the body