Extravasation management

This document provides a guide to health professionals for a comprehensive approach to the prevention, assessment and management of intravenous anti-cancer therapy extravasation. The information in this document should be used in conjunction with clinical expertise, the patient and local policies and procedures.

Clinicians require education prior to extravasation management- see  Extravasation eLearning for further information.

Definitions

Prevention strategies are key to reducing the risk of extravasation. Several strategies which reduce the risk of extravasation include:^rrrrrr

• educated and competent clinicians for vascular access device (VAD) management and safe administration of anti-cancer therapies
• informed patients: VAD insertion, prevention of extravasation
• standardised, evidence-based VAD selection, insertion, and management 
• safe administration of intravenous systemic anti-cancer therapies (refer to  Antineoplastic Drug Administration Course eLearning).

An extravasation kit containing instructions, materials and antidotes is stored in close proximity to patient care area where anti-cancer therapy is administered.

Refer to  Extravasation eLearning module for further information about prevention and  risk factors for extravasation.

Symptoms and signs^r

• discomfort, burning, stinging or pain
  • peripheral intravenous cannula (PIVC): distal to PIVC tip
  • central venous access device (CVAD): in the chest, neck, shoulder, arm or near the CVAD
• local swelling, oedema, erythema, pruritis, leakage at the site
• increase in resistance during administration
• alteration or slowing of flow rate, or alarming of infusion pump if being used (CVAD administration)
• sluggish or absence of blood return from VAD.

Signs of extravasation can be immediate but may be delayed for days to weeks. Late symptoms of an extravasation injury include inflammation, discolouration, induration and/or blistering.

Assessment criteria

In the event of an extravasation, the following factors are assessed:

• drug, dose administered, concentration, volume
• position and size of injury
• presence and degree of swelling, erythema
• severity of pain
• amount and type of exudate.

Link to the Extravasation assessment and documentation tool.

Extravasation from a CVAD

In the event of a suspected extravasation from a CVAD, flow studies may assist in diagnosis and location of the damage, leak, fracture or a malpositioned non-coring needle for a totally implantable venous access device (TIVAD).

Grading

Adapted from © Kim et al 2020^r

Extravasation management includes:^rrrr

Primary actions: SLAP

Secondary actions

• call for assistance
• complete assessment of affected area
• collect extravasation kit
• outline affected area with marker pen
• photograph affected area for medical record
• initiate appropriate drug specific management measures.

Conservative management^rrrrrrrr

• antidotes including dimethyl sulfoxide (DMSO) 99% solution, hyaluronidase, dexrazoxane. Refer to Quicklink summary table - treatments for extravasation of intravenous anti-cancer therapies for a comprehensive list of antidotes.
• topical thermal applications: warm and cold packs
• pain relief as required
• limb mobilisation.

Surgical management

• There is no optimal timeframe for referral to specialist surgical, plastics, wound care or other members of the healthcare team. Referral is based on the individual extravasation and patient.
• Possible indications:
  • vesicant extravasations
  • extravasations that involve a damaged CVAD
  • development of pain or delayed healing affected area
  • large volume extravasations.

Refer to Clinical procedure - extravasation management of intravenous anti-cancer therapies for more detailed information about extravasation management.

Clinical management includes:^r

• regular assessment of affected area
• regular review of pain management
• referral to members of the healthcare team as indicated e.g. surgery, pain management, wound management
• replace items from extravasation kit (including antidotes) from pharmacy if required.

Documentation

A suspected or actual extravasation is documented including the drug/solution, assessment findings, interventions, patient response, education and post-acute management planning using a standardised tool e.g. Extravasation assessment and documentation tool.

Patient education continues into the post-acute management phase including:

• treatment given and ongoing management required
• regular assessment & photography of the affected area
• notify medical team immediately or attend emergency department with signs/symptoms of infection
• verbal and written information. Refer to patient information sheets Care at home after an extravasation injury: Cold or warm pack and Care at home after an extravasation injury: DMSO and cold pack.

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Bibliography

Bairey, O., J. Bishara, B. Stahl, et al. 1997. "Severe tissue necrosis after cisplatin extravasation at low concentration: possible "immediate recall phenomenon"." J Natl.Cancer Inst. 89(16):1233-1234.

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Barutca, S., G. Kadikoylu, Z. Bolaman, et al. 2002. "Extravasation of paclitaxel into breast tissue from central catheter port." Support Care Cancer. 10(7):563-565.

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A 53-year-old woman with advanced-stage ovarian cancer experienced extravasation of paclitaxel into the breast tissue as a result of inappropriate needle insertion and/or dislodgement; it came from a central catheter port (CCP) that was found to be intact under radiological examination with contrast material. The breast became tender and oedematous with erythema, and local warming was observed within a few hours. The patient improved in the next few days during nonsteroidal anti-inflammatory medication and close observation, and the breast healed with thickened and darkened skin and central scarring in the 6th month of follow-up. To the best of our knowledge, extravasation into breast tissue is rare in the literature. Extravasation of vesicant drugs from CCP can cause tissue necrosis; it is therefore essential that ports be carefully assessed and used by experienced staff to lessen the likelihood of such an unpleasant complication.

Berghammer, P., R. Pohnl, M. Baur, et al. 2001. "Docetaxel extravasation." Support Care Cancer. 9(2):131-134.

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We report on an accidental extravasation of docetaxel given intravenously as chemotherapy in a cancer patient. The extravasate was immediately diluted subcutaneously with saline, in addition to which hypothermia (ice-packs) was implemented and topical dimethylsulfoxide (DMSO) was applied three times every 45 min. Corticosteroids and diclofenac were also administered. Dermatitis developed immediately but had disappeared within 24 h. Notably, dermatopathological changes were absent on days 2-4, minimal on day 5, and increased thereafter. Dermatitis developed as a late symptom, resulting in brown discoloration and skin hyperplasia. No plastic surgical intervention was necessary. We propose that isotonic saline, topical DMSO and local hypothermia may have restricted the inflammation and tissue necrosis induced by the extravasation of docetaxel. Repetitive topical application of DMSO beyond the day of extravasation had no additional benefit

Bertelli, G., D. Dini, G. B. Forno, et al. 1994. "Hyaluronidase as an antidote to extravasation of Vinca alkaloids: clinical results." J Cancer Res.Clin Oncol. 120(8):505-506.

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Skin necrosis is a recognized potential consequence of an inadvertent extravasation of Vinca alkaloids in the surrounding tissues during i.v. administration. Experimental studies suggest that hyaluronidase, an enzyme that degrades hyaluronic acid and improves the absorption of locally injected drugs, can reduce the risk of progressing to skin necrosis. On this basis, we used this enzyme as a local treatment after extravasations of Vinca alkaloids in seven patients. No patient suffered from subsequent skin necrosis. To the best of our knowledge, this is the first clinical report confirming the positive findings of experimental studies on the effectiveness of this antidote.

Bertelli, G., M. A. Cafferata, A. Ardizzoni, et al. 1997. "Skin ulceration potential of paclitaxel in a mouse skin model in vivo." Cancer. 79(11):2266-2269.

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Boyle, D. M. and C. Engelking. 1995 "Vesicant extravasation: myths and realities." Oncol Nurs Forum 22(1):57-67.

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PURPOSE/OBJECTIVES: To provide a comprehensive review of the literature pertinent to the phenomenon of antineoplastic vesicant extravasation within the framework of common misconceptions held by oncology nurses. DATA SOURCES: National guidelines, published articles in professional specialty journals and proceedings, and the authors' clinical experiences in the care of patients receiving vesicant agents. DATA SYNTHESIS: Antineoplastic vesicant extravasation can result in significant morbidity, severely limiting quality of life for patients with cancer. It also is a liability concern for oncology nurses. Many unanswered questions regarding extravasation exist because the phenomenon is difficult to study in humans and actual extravasation injuries are both sporadic and underreported. The incidence of extravasation from vascular access devices is unknown. Similarly, many recommended management strategies are empirically based. Misconceptions about the nature of extravasation injuries and the manner in which they should be managed contribute to poor patient outcomes and increased liability. CONCLUSIONS: The disproval of 10 myths regarding the nature and management of vesicant extravasation is an adjunctive step in the translation of existing national guidelines to workable institutional standards and appropriate professional practice. NURSING IMPLICATIONS: Oncology nurses are in a strategic position to observe the feasibility and efficacy of prevention and management guidelines established at national and local levels. Oncology nurses involved in the administration of antineoplastic vesicant agents are responsible for maintaining a current knowledge base about vesicants and for planning nursing care within the established standards of practice.

Comas, D. and J. Mateu. 1996. "Treatment of extravasation of both doxorubicin and vincristine administration in a Y-site infusion." Ann.Pharmacother. 30(3):244-246.

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OBJECTIVE: To describe a patient treated with vincristine, doxorubicin, and dexamethasone who experienced extravasation of both doxorubicin and vincristine during a Y-site infusion. CASE SUMMARY: A 74-year-old white woman was diagnosed with multiple myeloma IgA kappa in stage IIA. One year after a complete remission she relapsed. Her treatment included daily doxorubicin 16 mg in 500 mL of dextrose 5% and vincristine 0.4 mg in 500 mL of dextrose 5% administered in a Y-site continuous infusion into a peripheral vein of her left forearm. Extravasation occurred during administration of these drugs. Immediately, chondroitinsulfatase, a mucopolysaccharidase similar to hyaluronidase, was administered subcutaneously around the extravasation area and repeated 24 hours later. Furthermore, dimethyl sulfoxide 90% v/v was applied topically on the area four times daily for 2 weeks. All inflammatory signs resolved and no necrosis developed. DISCUSSION: Ths is the first report of an extravasation of two cytotoxic drugs. Doxorubicin and vincristine have different antidotes and opposite physical treatments for their extravasation. The antidotes dimethyl sulfoxide and chondroitinsulfatase have different mechanisms of action, but both cause uptake of the cytotoxic agent from the tissue and are likely to be administered together. No warming or cooling was performed. CONCLUSIONS: Topical dimethyl sulfoxide four times daily for 14 days plus subcutaneous chondroitinsulfatase in one or two applications effectively treated an extravasation of both doxorubicin and vincristine in our patient

Correspondence with Roche Australia, April 2022.

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Davis, M. E., D. DeSantis and K. Klemm. 1995. "A flow sheet for follow-up after chemotherapy extravasation." Oncol Nurs Forum 22(6):979-983.

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PURPOSE/OBJECTIVES: To introduce and describe the development and implementation of a flow sheet used to document patient follow-up after chemotherapy extravasation. DATA SOURCES: Published articles, institutional standards of nursing practice, and the Oncology Nursing Society Cancer Chemotherapy Guidelines. DATA SYNTHESIS: Extravasation is a potentially serious and severe complication of vesicant chemotherapy administration. A tool was designed to streamline documentation of patient symptoms, nursing interventions, patient education, and follow-up care after a suspected or actual extravasation. CONCLUSIONS: The flow sheet improves nursing documentation after a suspected or actual vesicant chemotherapy extravasation and provides a consistent, concise method for monitoring extravasations over time. IMPLICATIONS FOR NURSING PRACTICE: The flow sheet standardizes nursing assessment, intervention, patient education, and follow-up care after a suspected or actual chemotherapy extravasation. Use of the flow sheet saves time and improves consistency of nursing documentation.

de Lemos, M. L. and S. Walisser. 2005. "Management of extravasation of oxaliplatin." J Oncol Pharm.Pract. 11(4):159-162.

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Oxaliplatin extravasation has been associated with local pain and inflammation which may be severe and lead to complications including necrosis. Recent case reports suggest that oxaliplatin may be better classified as an irritant when extravasated. The optimal management of oxaliplatin extravasation however remains uncertain. Cold compress may cause local vasoconstriction and reduce cellular injury. However, it may potentially precipitate or worsen peripheral neuropathy. Warm compress may increase drug removal by local vasodilation and avoid peripheral neuropathy. However, it may potentially increase cellular uptake and hence injury. Further research into this area is needed.

Dorr, R. T. 1990. "Antidotes to vesicant chemotherapy extravasations." Blood Rev. 4(1):41-60.

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The foregoing sections have reviewed the experimental studies and clinical anecdotes describing potential pharmacologic antidotes to extravasations of vesicant anticancer agents. Numerous prior reviews have also suggested specific antidotes or very conservative, non-pharmacologic approaches. Many antidotal approaches to extravasation have not been experimentally validated and thus, few 'antidotes' share a rationale which is founded on positive experimental and clinical studies. However, using this criteria, a few active antidotes can be distilled from the literature. These are outlined in Table 6. These antidotes include isotonic (1/6 M) sodium thiosulfate for mechlorethamine (and optionally for cisplatin), hyaluronidase for the vinca alkaloids (and optionally for epipodophyllotoxins such as etoposide), and cooling with very topical DMSO and low dose hydrocortisone for the anthracyclines. For the alkylating agent mitomycin C, topical DMSO has been effective experimentally but has not yet received clinical validation, at least in published studies. Nonetheless, the severity of mitomycin C ulcerations and the documented safety of topical DMSO in the small series of doxorubicin extravasation patients argues for its use when mitomycin extravasates in the clinic. Furthermore, except for DMSO, all of these extravasation antidotes are listed in the official FDA-approved package inserts for each vesicant agent. Thus, the inserts for vincristine and vinblastine specify hyaluronidase, for doxorubicin, glucocorticosteroids, and for mechlorethamine, sodium thiosulfate. New studies are clearly needed to clarify the role of topical DMSO with anthracyclines and mitomycin C. In addition, efforts should be made to begin clinical development of radical dimers such as DHM3 which can directly inactivate quinone-containing vesicants like doxorubicin and mitomycin C. Although the incidence of chemotherapy extravasation may be lessened with vascular access devices, it nonetheless, continues to comprise a serious and highly litigious area of oncology practice. This commands continued extravasation intervention studies and diligent prevention when ever possible.

El Saghir, N. S. and Z. K. Otrock. 2004. "Docetaxel extravasation into the normal breast during breast cancer treatment." Anticancer Drugs. 15(4):401-404.

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We report a new case of central line extravasation of docetaxel into the normal breast of a patient with metastatic left breast cancer. During the infusion of docetaxel, the patient complained of mild discomfort at the site of a subclavian Port-a-Cath, followed by redness, warmth and itchiness of the entire skin of the right breast beneath the port of entry, and it involved the entire right breast by the next day. Over the following few days, she developed blistering, desquamation and oozing of serous fluid through skin fissures. Anti-histamines and hydrocortisonebased ointment induced partial relief of symptoms. Warm soaks induced skin relief. Reaction resolved over few weeks leaving a brownish pigmentation of the skin of the breast, with clearly demarcated lines, as the only sequlae.

Ener, R. A., S. B. Meglathery and M. Styler. 2004. "Extravasation of systemic hemato-oncological therapies." Ann Oncol 15(6):858-862.

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Systemic intravenous chemotherapeutic agents can cause multiple emergency situations including acute and chronic local and systemic reactions. Amongst them, drug extravasation is one of the most devastating complications, as many drugs can cause varying degrees of local tissue injury when extravasated. Although it is difficult to give an accurate measurement, the incidence of extravasation of systemic infusional chemotherapeutic agents has been reported to occur in 0.1-6.5% of cases. Since most extravasations can be prevented with the systematic implementation of careful administration techniques, guidelines have been published for the administration of vesicant drugs. The proper maintenance of intravenous lines, application of local cooling or warming for certain extravasations, and the use of antidotes to prevent the local toxic action of the extravasated drugs are the basis of medical management. The specific antidotes for certain chemotherapeutic agents are also discussed in this article.

Extravasation. In: IBM Micromedex® Disease General Medicine (electronic version). IBM Watson Health, Greenwood Village, Colorado, USA. Available at: https://www.micromedexsolutions.com.acs.hcn.com.au (accessed November 2021).

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Froiland, K. 2007. "Extravasation injuries: implications for WOC nursing." J Wound.Ostomy.Continence.Nurs. 34(3): 299-302.

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Hadaway, L. C. 2004. "Preventing and managing peripheral extravasation." Nursing 34(5):66-67.

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Hadaway, L. C. 2004. "Preventing extravasation from a central line." Nursing 34(6): 22-3.

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Jones, L. and P. Coe. 2004. "Extravasation." Eur J Oncol Nurs 8(4):355-358.

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Kennedy, J. G., J. P. Donahue, B. Hoang, et al. 2003. "Vesicant characteristics of oxaliplatin following antecubital extravasation." Clin Oncol (R.Coll.Radiol.). 15(5):237-239.

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Oxaliplatin is a novel class of platinum chermotherapeutic agent used in refractory adenocarcinoma. It has previously been regarded as a non-vesicant, and as such was considered safe to administer through peripheral veins. This report documents severe muscle and subcutaneous reaction with a single dose of oxaliplatin at the site of extravasation in a patient aged 58 years. Conventional therapeutic modalities were employed to reduce the effect of the soft tissue infiltrate. Despite that, significant muscle necrosis and fibrosis occurred. Surgery was deferred secondary to patient choice, and eventual extensive physical therapy restored function to the elbow joint. This case shows that oxaliplatin may not be an appropriate cytotoxic agent to be administered through a peripheral line and consideration must be made for central access when this drug is used. In addition, when extravasation does occur, the current report indicates that non-surgical management can be successful.

Kimmel, J., P. Fleming, S. Cuellar et al. 2018. “Pharmacological management of anticancer agent extravasation: A single institutional guideline.” J Oncol Pharm Pract. 24(2):129-138.

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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 extravasations, 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 ambulatory 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.

Levin, M., D. Caravone and C. Geiser. 1996. "Mitoxantrone extravasation and tissue necrosis." Am J Health Syst.Pharm. 53(10):1192, 1194.

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Loth, T. S. and W. W. Eversmann, Jr. 1986. "Treatment methods for extravasations of chemotherapeutic agents: a comparative study." J Hand Surg Am 11(3):388-396.

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A rat model was used to compare early surgical intervention with injectable and topical antidotes with regard to their effectiveness in preventing cutaneous ulcers that were caused by intradermal injections of vesicant chemotherapeutic agents. The (animals) rats received bilateral flank injections of doxorubicin, vincristine, actinomycin D, mitomycin C, or carmustine (BCNU) in concentrations that were comparable to concentrations used for human patients; after the injections they underwent debridement at various intervals or received immediate applications of selected antidotes. Many antidotes which were frequently used, were not effective in limiting the size of the ulcer and in producing rapid healing of ulcers that were caused by experimental vesicant extravasations. Early surgical debridement was the most effective method of decreasing vesicant ulcer size and facilitating rapid ulcer healing of all the interventions tested.

Ludwig, C. U., H. R. Stoll, R. Obrist, et al. 1987. "Prevention of cytotoxic drug induced skin ulcers with dimethyl sulfoxide (DMSO) and alpha-tocopherole." Eur J Cancer Clin Oncol 23(3):327-329.

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Accidental subcutaneous extravasation of several antineoplastic agents may provoke skin ulcerations for which there has been no simple and effective treatment. Since January 1983 we have treated all patients in our institution sustaining extravasation by a cytotoxic drug with a combination of DMSO and alpha-Tocopherole. During the first 48 hr after extravasation a mixture of 10% alpha-Tocopherole acetate and 90% DMSO was topically applied. The bandage was changed every 12 hr. So far eight patients with extravasation of an anthracycline or Mitomycin were treated on this protocol. No skin ulceration, functional or neurovascular impairment occurred in any of these patients. The only toxic effect observed by this treatment was a minor skin irritation. The combination of DMSO and alpha-Tocopherole seems to prevent skin ulceration induced by anthracyclines and Mitomycin.

Luke, E. 2005. "Mitoxantrone-induced extravasation." Oncol Nurs.Forum. 32(1):27-29.

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Madhavan, S. and D. W. Northfelt. 1995. "Lack of vesicant injury following extravasation of liposomal doxorubicin." J Natl.Cancer Inst. 87(20):1556-1557.

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Maslovsky, I. 2007. "Extravasation injury as a result of VAD chemotherapy." J Wound.Ostomy.Continence.Nurs. 34(3):297-298.

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Mateu, J., M. Alzamora, M. Franco, et al. 1994. "Ifosfamide extravasation." Ann.Pharmacother. 28(11):1243-1244.

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OBJECTIVE: To report a case in which a local reaction is attributed to an ifosfamide extravasation. Previously, extravasated ifosfamide has been considered a nonirritant. CASE SUMMARY: A 54-year-old woman with a non-Hodgkin's lymphoma in stage IV B developed a local reaction in her right arm after an ifosfamide extravasation. No pressure was prescribed, no bandaging was applied on the affected area, and the limb was elevated to the heart level. In addition, chondroitinsulfatase 150 turbidity-reducing units was administered subcutaneously around the area. This procedure was repeated 12 hours later, resulting in a satisfactory decrease in the inflammatory signs and pain. DISCUSSION: The local reaction in the patient's arm cannot be attributed to the hypertonicity of the infusing solution or to the vehicle of the infusate. The antidote used was chondroitinsulfatase, an enzyme similar to hyaluronidase. It enhances the systemic uptake of the drug from the tissue. CONCLUSIONS: Extravasated ifosfamide is a potential irritant. General measures applied after its extravasation can be potentiated strongly by local subcutaneous administration of chondroitinsulfatase or hyaluronidase, repeated if necessary.

Micromedex® (electronic version): Dexrazoxane Hydrochloride. IBM Watson Health, Greenwood Village, Colorado, USA. Available at: https://www.micromedexsolutions.com.acs.hcn.com.au/ [accessed November 2021]

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MIMSOnline Prescribing information: Brentuximab vedotin. © 2022 MIMS Australia Pty Ltd. [Accessed April 2022]

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MIMSOnline Prescribing information: DBL Cisplatin Injection. © 2021 MIMS Australia Pty Ltd. [Accessed November 2021]

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MIMSOnline Prescribing information: Sacituzumab govitecan. © 2022 MIMS Australia Pty Ltd. [Accessed May 2022]

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Nesti, S. P. and R. Kovac. 2000. "5-fluorouracil extravasation following port failure." J Intraven.Nurs. 23(3):176-180.

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A case is presented of cytotoxic extravasation as a result of an implantable venous port being perforated by a standard Huber needle. A patient receiving 5-fluorouracil via a dual reservoir port, implanted within the left chest wall, presented with hemoserous discharge from the right needle entry site. The left chest wall was warm to touch, erythematous, and swollen. Subcutaneous infiltration was suspected, and the infusion was ceased. A venogram was performed demonstrating significant extravasation around the left reservoir only. On port removal, inspection showed the Huber needle had penetrated the base plate on the left side. It is recommended that this complication be added as a possible sequelae of central venous port use.

NSW Health. 2005. Consent to Medical Treatment - Patient Information. PD2005_406. NSW Department of health.

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NSW Health. 2007. Infection Control Policy PD2007_36. NSW Department of Health 2007

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Olver, I. N. and M. A. Schwarz. 1983. "Use of dimethyl sulfoxide in limiting tissue damage caused by extravasation of doxorubicin." Cancer Treat Rep 67(4):407-408.

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Olver, I. N., J. Aisner, A. Hament, et al. 1988. "A prospective study of topical dimethyl sulfoxide for treating anthracycline extravasation." J Clin Oncol 6(11):1732-1735.

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Twenty patients with extravasation of anthracyclines were treated on a single-arm pilot study with topical 99% dimethyl sulfoxide (DMSO) and observed for 3 months with regular examinations and photographs. DMSO was applied to approximately twice the area affected by the extravasation and allowed to air dry. This was repeated every six hours for 14 days. The initial signs of extravasation included swelling in 17 patients, erythema in 15, and pain in 12. The median area of damage was 8.25 cm2 and a median of 25 minutes elapsed between extravasation and application of DMSO with one patient not treated until seven days postextravasation. Sixteen patients were observed for 3 months, two died of disease earlier after receiving 2 weeks of DMSO and three days of DMSO, respectively, and two were lost to follow-up having received one day and five days of DMSO. In no patient did extravasation progress to ulceration or require surgical intervention, suggesting with 95% confidence a true ulceration rate of between 1% and 17%. At 3 months there was no sign of residual damage in six patients, while a pigmented indurated area remained in ten. Two patients had a recall reaction with increased pain at the extravasation site when further intravenous (IV) doxorubicin was administered. The only toxicities of DMSO included a burning feeling on application subsequently associated with itch, erythema, and mild scaling. Blisters occurred in four patients. Six patients reported a characteristic breath odor associated with DMSO. Topical DMSO appears to be a safe and effective treatment for anthracycline extravasation.

Payne, AS et al. 2018. "Extravasation Injury from Chemotherapy and other non-antineoplastic vesicants. In UpToDate (accessed 2019)

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Raley, J., J. P. Geisler, T. E. Buekers, et al. 2000. "Docetaxel extravasation causing significant delayed tissue injury." Gynecol.Oncol. 78(2):259-260.

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PURPOSE: Docetaxel is a relatively new taxane that has not been associated with significant tissue injury after extravasation. We present a case of a patient who had grade 4 tissue toxicity after extravasation of docetaxel infused through a peripheral intravenous site. CASE REPORT: A 71-year-old female was being treated for recurrent ovarian cancer with docetaxel and carboplatin. Shortly after the docetaxel infusion began, she experienced docetaxel extravasation into the dorsum of her left hand. The infusion was halted, and then the administration was continued in a peripheral intravenous site in the other upper extremity. Erythema was noted by the patient on the dorsum of her left hand 6 days after infiltration. The following day, the patient noted severe pain, decreased function, and blistering along with increased erythema. The patient presented to the gynecology oncology clinic 11 days after the extravasation injury occurred. Conservative management was undertaken, and over the next 4 weeks the patient had resolution of the skin changes and full return of function. CONCLUSION: Docetaxel can cause significant delayed tissue injury if extravasation occurs.

Reeves, D. 2007. "Management of anthracycline extravasation injuries." Ann.Pharmacother. 41(7):1238-1242.

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OBJECTIVE: To review the evidence for the management of anthracycline extravasation and determine the optimal treatment of such injuries. DATA SOURCES: A search of MEDLINE (1966-February 2007) and International Pharmaceutical Abstracts (1970-February 2007) was performed using the search terms anthracyclines and extravasation. DATA SYNTHESIS: Extravasation of anthracyclines can have devastating effects. After infiltration of these drugs into the interstitial tissue, damage may range from mild erythema and pain to severe tissue necrosis. Many agents have been studied in the management of these injuries; however, few have demonstrated efficacy and treatment remains controversial. Nonpharmacologic modalities shown to limit extravasation injuries include local tissue cooling and elevation of the affected area. Corticosteroids, sodium bicarbonate, hyaluronidase, hyperbaric oxygen, heparin fractions, alpha-tocopherol, N-acetylcysteine, and granulocyte macrophage-colony stimulating factor have all either been shown to be ineffective or have limited data supporting their use. Topical dimethyl sulfoxide (DMSO) has been shown in prospective studies to limit the course of extravasation injuries. Dexrazoxane has been shown in animal models and case reports to be useful in the management of anthracycline extravasation. Two recent prospective clinical trials examining intravenous dexrazoxane 1000 mg/m2 within 6 hours of extravasation, 1000 mg/m2 24 hours after extravasation, and 500 mg/m2 48 hours after extravasation injuries add to the data supporting the use of this agent in such injuries. Of the 54 patients enrolled, surgery-requiring necrosis was avoided in 98.2%. CONCLUSIONS: The optimal treatment of anthracycline extravasation includes local tissue cooling, elevation of the afflicted extremity, dexrazoxane administration, and possibly topical DMSO. Many other drugs have been investigated; however, due to a lack of data, they cannot be recommended for the management of anthracycline extravasation.

Rudolph, R. and D. L. Larson. 1987. "Etiology and treatment of chemotherapeutic agent extravasation injuries: a review." J Clin Oncol 5(7):1116-1126.

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While extravasation from intravenous (IV) lines is common and usually benign, leakage of certain drugs can cause severe skin ulceration. These ulcerogenic drugs can be conveniently divided into two categories, depending on whether they bind to DNA. Chemotherapeutic agents such as doxorubicin, which bind to DNA, are especially prone to cause severe extravasation skin ulcers. These ulcers are often chronic and progressive. Neither clinical nor experimental studies have shown an antidote to doxorubicin extravasation, which is best prevented by careful technique. If extravasation is suspected, the infusion should be immediately stopped. In the event of extravasation, elevation and ice are the currently recommended treatment. While small ulcerations may on occasion heal, large ulcerations require surgical excision for relief of pain and salvage of underlying tissues.

SafeWork NSW. 2017. Cytotoxic Drugs and Related Waste Risk Management Guide.

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Saini, A., A. Berruti, P. Sperone, et al. 2006. "Recall inflammatory skin reaction after use of pegylated liposomal doxorubicin in site of previous drug extravasation." Lancet Oncol. 7(2):186-187.

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Schrijvers, D. L. 2003. "Extravasation: a dreaded complication of chemotherapy." Ann Oncol 14 Suppl 3:iii26-30.

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Schulmeister, L. 2005. "Article on mitoxantrone-induced extravasation raised useful questions." Oncol Nurs.Forum. 32(4): 719-720.

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Schulmeister, L. and D. Camp-Sorrel. 2000. "Chemotherapy extravasation from implanted ports." Oncol Nurs.Forum. 27(3): 531-538.

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PURPOSE/OBJECTIVES: To describe the four primary causes of extravasation from implanted ports. DATA SOURCES: Journal articles, textbooks, medical records, depositions, serial photographs, and the authors' personal experiences. DATA SYNTHESIS: Extravasation from ports can occur by four major mechanisms: incomplete needle placement and needle dislodgment, thrombus or fibrin sheath formation, perforation of the superior vena cava, and catheter fracture. The degree of tissue injury can vary but may be severe enough to require that a simple mastectomy be performed to manage chest wall necrosis. CONCLUSIONS: Extravasation is a known risk of chemotherapy administration via implanted ports. Vesicants should be administered only after a blood return has been obtained and the needle inserted into the port septum has been adequately secured. IMPLICATIONS FOR NURSING PRACTICE: Extravasation of vesicant drugs from ports can cause tissue necrosis and may prompt litigation. Risk-management strategies include careful assessment and use of ports, comprehensive patient teaching about the risk of extravasation and measures to decrease the likelihood of needle dislodgment, and development of extravasation-management policies that address port extravasations.

Stanford, B. L. and F. Hardwicke. 2003. "A review of clinical experience with paclitaxel extravasations." Support Care Cancer. 11(5):270-277.

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Paclitaxel is a novel anti-neoplastic with a wide spectrum of activity in various malignant tumors. Extravasation of chemotherapy drugs is a widely feared adverse event in oncology patients. A Medline search between 1966 and October 2002 was conducted to identify case reports related to paclitaxel extravasation, as well as a bibliography screening of identified papers. The goal of this work is to summarize the available reports of paclitaxel extravasation and assess its vesicant potential. Additionally, management strategies for extravasation events due to paclitaxel are assessed.

Valencak, J., M. Troch and M. Raderer. 2007. "Cutaneous recall phenomenon at the site of previous doxorubicin extravasation after second-line chemotherapy." J Natl.Cancer Inst. 99(2):177-178.

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Viale, P. H. 2003. "Complications associated with implantable vascular access devices in the patient with cancer." J Infus.Nurs. 26(2):97-102.

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Implantable vascular access devices (IVADs), or implantable ports, have been used for patients with cancer for more than 20 years. Although these devices have greatly improved infusion access for this population of patients, complications may still occur. Nurses working with oncology patients who have IVADs must be aware of possible problems for these patients, as well as the importance of early assessment and intervention. The diagnosis of cancer and potential treatments for this disease may make these patients at higher risk for complications associated with the use of IVADS.

Viale, P. H. 2006. "Chemotherapy and cutaneous toxicities: implications for oncology nurses." Semin.Oncol Nurs. 22(3):144-151.

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OBJECTIVE: To review common cutaneous effects and dermatologic or cutaneous toxicities related to the administration of chemotherapy. These range from mostly cosmetic, such as hyperpigmentation or alopecia, to dose-limiting toxicities such as palmar-plantar erythrodysesthesia or hand-foot syndrome. DATA SOURCES: Current research, published literature, and internet resources. CONCLUSION: Assessment and grading of associated toxicities of therapy is an integral part of caring for this patient population. Early intervention may reduce toxicities associated with therapies for this patient population IMPLICATIONS FOR NURSING PRACTICE: As more patients receive chemotherapy, dermatologic effects are becoming more common. Oncology nurses must be skilled in managing these side effects

Wickham, R., C. Engelking, C. Sauerland, et al. 2006. "Vesicant extravasation part II: Evidence-based management and continuing controversies." Oncol Nurs.Forum. 33(6):1143-1150.

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PURPOSE/OBJECTIVES: To review the literature, synthesize current recommendations, and discuss remaining controversies regarding vesicant extravasation management. DATA SOURCES: Published evidence-based reports, clinical articles, and anecdotal case reports about antineoplastic and nonantineoplastic vesicant agent management. DATA SYNTHESIS: Prevention of vesicant extravasation sequelae requires knowledge about vesicant extravasation manifestations and differentiation of vesicant extravasation from other local IV site reactions. When evidence is weak or missing, logical application of data-based or empirical management strategies is critical. Actions may include timely administration of subcutaneous or topical antidotes, comfort measures, and surgical interventions to minimize the extent of tissue damage and morbidity should extravasation occur. CONCLUSIONS: Vesicant extravasation and sequelae constitute a complex patient problem. Clinicians should strive to prevent extravasation or seek to minimize injury should it occur. To this end, clinicians must demonstrate awareness of its risks and use specialized knowledge when administering vesicant agents. IMPLICATIONS FOR NURSING: Nurses who administer vesicant agents should understand the nursing and collaborative actions that should be taken to minimize patient morbidity, pain, and disability.

Wood, L. S. and S. M. Gullo. 1993. "IV vesicants: how to avoid extravasation." Am J Nurs 93(4):42-46.

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