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Extravasation injury from chemotherapy and other non-antineoplastic vesicants

Aimee S Payne, MD, PhD
Jan Buter, MD, PhD
Section Editor
Reed E Drews, MD
Deputy Editor
Diane MF Savarese, MD


Extravasation refers to the escape of a drug into the extravascular space, either by leakage from a vessel or by direct infiltration [1]. Although many drugs are irritating when they are introduced into extravascular tissues, extravasation of a vesicant drug has the potential to cause tissue damage with severe and/or lasting injury. Although the most well-known vesicants are cytotoxic chemotherapy drugs (table 1), several non-antineoplastic drugs also have vesicant properties (table 2).

The incidence, risk factors, clinical presentation, prevention, and management of extravasation injury from chemotherapy and non-antineoplastic vesicants are reviewed here, with a focus on chemotherapy extravasation injury. Other cutaneous complications of chemotherapy and venous irritation (chemical phlebitis) that occurs with drug administration into an intact vein (as is seen predominantly with vinorelbine and epirubicin) are discussed elsewhere. (See "Cutaneous side effects of conventional chemotherapy agents".)


Incidence — The true incidence of chemotherapy vesicant extravasation is unclear since there is no central reporting mechanism. With an increasing awareness of the risks from extravasation, the frequency appears to have fallen.

Data from MD Anderson Cancer Center indicate that the rate of serious extravasation injury (as determined by referral patterns to a plastic surgery clinic) declined from 0.1 to 0.01 percent over a 15-year period, based upon individual doses of chemotherapy administered [2]. However, this series only includes patients who were referred to plastic surgery, rather than all extravasations, while the denominator includes all individual doses of chemotherapy delivered over the six-year study period. As such, this rate probably underestimates the true incidence of chemotherapy extravasation injury. Furthermore, this rate may not reflect the actual rate in other clinical settings.

Infusional administration of vesicant antineoplastic agents is frequently done through a central venous access device (CVAD) to minimize the likelihood of subcutaneous extravasation. While the risk of chemotherapy extravasation through a CVAD is small, it is not zero, and extravasation may be due to injection technique or device failure:

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Literature review current through: Nov 2017. | This topic last updated: Aug 31, 2017.
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  1. Fischer D, Knobf M, Durivage H. The Cancer Chemotherapy Handbook, Mosby, 1997. p.514.
  2. Langstein HN, Duman H, Seelig D, et al. Retrospective study of the management of chemotherapeutic extravasation injury. Ann Plast Surg 2002; 49:369.
  3. Biffi R, Pozzi S, Agazzi A, et al. Use of totally implantable central venous access ports for high-dose chemotherapy and peripheral blood stem cell transplantation: results of a monocentre series of 376 patients. Ann Oncol 2004; 15:296.
  4. Yildizeli B, Laçin T, Batirel HF, Yüksel M. Complications and management of long-term central venous access catheters and ports. J Vasc Access 2004; 5:174.
  5. Narducci F, Jean-Laurent M, Boulanger L, et al. Totally implantable venous access port systems and risk factors for complications: a one-year prospective study in a cancer centre. Eur J Surg Oncol 2011; 37:913.
  6. Goolsby TV, Lombardo FA. Extravasation of chemotherapeutic agents: prevention and treatment. Semin Oncol 2006; 33:139.
  7. Schulmeister L. Extravasation management: clinical update. Semin Oncol Nurs 2011; 27:82.
  8. Doellman D, Hadaway L, Bowe-Geddes LA, et al. Infiltration and extravasation: update on prevention and management. J Infus Nurs 2009; 32:203.
  9. 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.
  10. Schulmeister L, Camp-Sorrell D. Chemotherapy extravasation from implanted ports. Oncol Nurs Forum 2000; 27:531.
  11. Perez Fidalgo JA, Garcia Fabregat L, Cervantes A, et al. Management of chemotherapy extravasation: ESMO-EONS Clinical Practice Guidelines. Ann Oncol 2012; 23(7 Suppl): vii167.
  12. Kreidieh FY, Moukadem HA, El Saghir NS. Overview, prevention and management of chemotherapy extravasation. World J Clin Oncol 2016; 7:87.
  13. Baur M, Kienzer HR, Rath T, Dittrich C. Extravasation of Oxaliplatin (Eloxatin((R))) - Clinical Course. Onkologie 2000; 23:468.
  14. Foo KF, Michael M, Toner G, Zalcberg J. A case report of oxaliplatin extravasation. Ann Oncol 2003; 14:961.
  15. Kretzschmar A, Pink D, Thuss-Patience P, et al. Extravasations of oxaliplatin. J Clin Oncol 2003; 21:4068.
  16. Stanford BL, Hardwicke F. A review of clinical experience with paclitaxel extravasations. Support Care Cancer 2003; 11:270.
  17. Bicher A, Levenback C, Burke TW, et al. Infusion site soft-tissue injury after paclitaxel administration. Cancer 1995; 76:116.
  18. Barutca S, Kadikoylu G, Bolaman Z, et al. Extravasation of paclitaxel into breast tissue from central catheter port. Support Care Cancer 2002; 10:563.
  19. Ajani JA, Dodd LG, Daugherty K, et al. Taxol-induced soft-tissue injury secondary to extravasation: characterization by histopathology and clinical course. J Natl Cancer Inst 1994; 86:51.
  20. Herrington JD, Figueroa JA. Severe necrosis due to paclitaxel extravasation. Pharmacotherapy 1997; 17:163.
  21. Infusion-related complications. In: Chemotherapy and Biotherapy Guidelines and Recommendations for Practice, 4, Polovich M, Olsem M, LeFebvre KB (Eds), Oncology Nursing Society, Pittsburgh 2014. p.155.
  22. Schulmeister L. Extravasation. In: MASCC Textbook ofCancer Supportive Care and Cancer Survivorship, Olver, IN. (Eds), Springer, New York 2011. p.351.
  23. Luke E. Mitoxantrone-induced extravasation. Oncol Nurs Forum 2005; 32:27.
  24. Shafaee MN, Salahudeen AA, Valero V. Skin Necrosis After Ado-Trastuzumab Emtansine Extravasation. J Oncol Pract 2017; 13:555.
  25. Susser WS, Whitaker-Worth DL, Grant-Kels JM. Mucocutaneous reactions to chemotherapy. J Am Acad Dermatol 1999; 40:367.
  26. Usuki A, Funasaka Y, Oka M, Ichihashi M. Tegafur-induced photosensitivity--evaluation of provocation by UVB irradiation. Int J Dermatol 1997; 36:604.
  27. http://www.bardaccess.com/assets/literature/MC-0086-03_Critical_Choice_Irritants_Vesicants_Web.pdf (Accessed on March 09, 2017).
  28. Wang CL, Cohan RH, Ellis JH, et al. Frequency, management, and outcome of extravasation of nonionic iodinated contrast medium in 69,657 intravenous injections. Radiology 2007; 243:80.
  29. Loth TS, Eversmann WW Jr. Treatment methods for extravasations of chemotherapeutic agents: a comparative study. J Hand Surg Am 1986; 11:388.
  30. Shapiro J, Richardson GE. Paclitaxel-induced "recall" soft tissue injury occurring at the site of previous extravasation with subsequent intravenous treatment in a different limb. J Clin Oncol 1994; 12:2237.
  31. Meehan JL, Sporn JR. Case report of Taxol administration via central vein producing a recall reaction at a site of prior Taxol extravasation. J Natl Cancer Inst 1994; 86:1250.
  32. du Bois A, Kommoss FG, Pfisterer J, et al. Paclitaxel-induced "recall" soft tissue ulcerations occurring at the site of previous subcutaneous administration of paclitaxel in low doses. Gynecol Oncol 1996; 60:94.
  33. Valencak J, Troch M, Raderer M. Cutaneous recall phenomenon at the site of previous doxorubicin extravasation after second-line chemotherapy. J Natl Cancer Inst 2007; 99:177.
  34. Saini A, Berruti A, Sperone P, et al. Recall inflammatory skin reaction after use of pegylated liposomal doxorubicin in site of previous drug extravasation. Lancet Oncol 2006; 7:186.
  35. Wilson J, Carder P, Gooi J, Nishikawa H. Recall phenomenon following epirubicin. Clin Oncol (R Coll Radiol) 1999; 11:424.
  36. Kramer F, Schippert C, Rinnau F, et al. The First Description of Docetaxel-Induced Recall Inflammatory Skin Reaction After Previous Drug Extravasation. Ann Pharmacother 2011; 45:e11.
  37. Ley BD, Millán GG, Perez JS, et al. Docetaxel recall phenomenon at the site of previous drug extravasation. Arch Dermatol 2010; 146:1190.
  38. Bozkurt AK, Uzel B, Akman C, et al. Intrathoracic extravasation of antineoplastic agents: case report and systematic review. Am J Clin Oncol 2003; 26:121.
  39. Wickham R, Engelking C, Sauerland C, Corbi D. Vesicant extravasation part II: Evidence-based management and continuing controversies. Oncol Nurs Forum 2006; 33:1143.
  40. Harrold K, Gould D, Drey N. The management of cytotoxic chemotherapy extravasation: a systematic review of the literature to evaluate the evidence underpinning contemporary practice. Eur J Cancer Care (Engl) 2015; 24:771.
  41. Jacobson JO, Polovich M, McNiff KK, et al. American Society of Clinical Oncology/Oncology Nursing Society chemotherapy administration safety standards. Oncol Nurs Forum 2009; 36:651.
  42. Jacobson JO, Polovich M, Gilmore TR, et al. Revisions to the 2009 american society of clinical oncology/oncology nursing society chemotherapy administration safety standards: expanding the scope to include inpatient settings. J Oncol Pract 2012; 8:2.
  43. Neuss MN, Polovich M, McNiff K, et al. 2013 updated American Society of Clinical Oncology/Oncology Nursing Society chemotherapy administration safety standards including standards for the safe administration and management of oral chemotherapy. Oncol Nurs Forum 2013; 40:225.
  44. Pluschnig U, Haslik W, Bayer G, et al. Outcome of chemotherapy extravasation in a large patient series using a standardised management protocol. Support Care Cancer 2015; 23:1741.
  45. Cox K, Stuart-Harris R, Abdini G, et al. The management of cytotoxic-drug extravasation: guide-lines drawn up by a working party for the Clinical Oncological Society of Australia. Med J Aust 1988; 148:185.
  46. Albanell J, Baselga J. Systemic therapy emergencies. Semin Oncol 2000; 27:347.
  47. Bertelli G. Prevention and management of extravasation of cytotoxic drugs. Drug Saf 1995; 12:245.
  48. Larson DL. What is the appropriate management of tissue extravasation by antitumor agents? Plast Reconstr Surg 1985; 75:397.
  49. Dorr RT, Alberts DS. Vinca alkaloid skin toxicity: antidote and drug disposition studies in the mouse. J Natl Cancer Inst 1985; 74:113.
  50. Ascherman JA, Knowles SL, Attkiss K. Docetaxel (taxotere) extravasation: a report of five cases with treatment recommendations. Ann Plast Surg 2000; 45:438.
  51. Theman TA, Hartzell TL, Sinha I, et al. Recognition of a new chemotherapeutic vesicant: trabectedin (ecteinascidin-743) extravasation with skin and soft tissue damage. J Clin Oncol 2009; 27:e198.
  52. Jordan K, Jahn F, Jordan B, et al. Trabectedin: Supportive care strategies and safety profile. Crit Rev Oncol Hematol 2015; 94:279.
  53. Langer SW, Sehested M, Jensen PB. Dexrazoxane is a potent and specific inhibitor of anthracycline induced subcutaneous lesions in mice. Ann Oncol 2001; 12:405.
  54. Jensen JN, Lock-Andersen J, Langer SW, Mejer J. Dexrazoxane-a promising antidote in the treatment of accidental extravasation of anthracyclines. Scand J Plast Reconstr Surg Hand Surg 2003; 37:174.
  55. Langer SW, Sehested M, Jensen PB. Treatment of anthracycline extravasation with dexrazoxane. Clin Cancer Res 2000; 6:3680.
  56. Langer SW, Sehested M, Jensen PB, et al. Dexrazoxane in anthracycline extravasation. J Clin Oncol 2000; 18:3064.
  57. Mouridsen HT, Langer SW, Buter J, et al. Treatment of anthracycline extravasation with Savene (dexrazoxane): results from two prospective clinical multicentre studies. Ann Oncol 2007; 18:546.
  58. Madhavan S, Northfelt DW. Lack of vesicant injury following extravasation of liposomal doxorubicin. J Natl Cancer Inst 1995; 87:1556.
  59. Curtit E, Chaigneau L, Pauchot J, et al. Extravasation of liposomal doxorubicin induces irritant reaction without vesicant injury. Anticancer Res 2012; 32:1481.
  60. Vos FY, Lesterhuis WJ, Brüggemann RJ, Graaf WT. Recovery of symptomatic extravasation of liposomal doxorubicin after dexrazoxane treatment. Anticancer Drugs 2012; 23:139.
  61. Tsavaris NB, Komitsopoulou P, Karagiaouris P, et al. Prevention of tissue necrosis due to accidental extravasation of cytostatic drugs by a conservative approach. Cancer Chemother Pharmacol 1992; 30:330.
  64. Dorr RT, Soble M, Alberts DS. Efficacy of sodium thiosulfate as a local antidote to mechlorethamine skin toxicity in the mouse. Cancer Chemother Pharmacol 1988; 22:299.
  65. HATIBOGLU I, MIHICH E, MOORE GE, NICHOL CA. Use of sodium thiosulfate as a neutralizing agent during regional administration of nitrogen mustard: an experimental study. Ann Surg 1962; 156:994.
  66. Dorr RT, Alberts DS, Einspahr J, et al. Experimental dacarbazine antitumor activity and skin toxicity in relation to light exposure and pharmacologic antidotes. Cancer Treat Rep 1987; 71:267.
  67. Owen OE, Dellatorre DL, Van Scott EJ, Cohen MR. Accidental intramuscular injection of mechlorethamine. Cancer 1980; 45:2225.
  68. Bertelli G, Dini D, Forno GB, et al. Hyaluronidase as an antidote to extravasation of Vinca alkaloids: clinical results. J Cancer Res Clin Oncol 1994; 120:505.
  69. Sokol DK, Dahlmann A, Dunn DW. Hyaluronidase treatment for intravenous phenytoin extravasation. J Child Neurol 1998; 13:246.
  70. Zenk KE, Dungy CI, Greene GR. Nafcillin extravasation injury. Use of hyaluronidase as an antidote. Am J Dis Child 1981; 135:1113.
  71. Cicchetti S, Jemec B, Gault DT. Two case reports of vinorelbine extravasation: management and review of the literature. Tumori 2000; 86:289.
  72. Kumar MM, Sprung J. The use of hyaluronidase to treat mannitol extravasation. Anesth Analg 2003; 97:1199.
  73. Wiegand R, Brown J. Hyaluronidase for the management of dextrose extravasation. Am J Emerg Med 2010; 28:257.e1.
  74. Pérez-Fidalgo JA, Cervantes A. Reply to 'Comment on: management of chemotherapy extravasation: ESMO-EONS clinical practice guidelines'. Ann Oncol 2013; 24:1129.
  75. Bertelli G, Gozza A, Forno GB, et al. Topical dimethylsulfoxide for the prevention of soft tissue injury after extravasation of vesicant cytotoxic drugs: a prospective clinical study. J Clin Oncol 1995; 13:2851.
  76. Olver IN, Aisner J, Hament A, et al. A prospective study of topical dimethyl sulfoxide for treating anthracycline extravasation. J Clin Oncol 1988; 6:1732.
  77. Monstrey SJ, Mullick P, Narayanan K, Ramasastry SS. Hyperbaric oxygen therapy and free radical production: an experimental study in doxorubicin (Adriamycin) extravasation injuries. Ann Plast Surg 1997; 38:163.
  78. Averbuch SD, Boldt M, Gaudiano G, et al. Experimental chemotherapy-induced skin necrosis in swine. Mechanistic studies of anthracycline antibiotic toxicity and protection with a radical dimer compound. J Clin Invest 1988; 81:142.
  79. Heitmann C, Durmus C, Ingianni G. Surgical management after doxorubicin and epirubicin extravasation. J Hand Surg Br 1998; 23:666.
  80. Larson DL. Treatment of tissue extravasation by antitumor agents. Cancer 1982; 49:1796.
  81. Rudolph R, Larson DL. Etiology and treatment of chemotherapeutic agent extravasation injuries: a review. J Clin Oncol 1987; 5:1116.
  82. Boyle DM, Engelking C. Vesicant extravasation: myths and realities. Oncol Nurs Forum 1995; 22:57.
  83. Scuderi N, Onesti MG. Antitumor agents: extravasation, management, and surgical treatment. Ann Plast Surg 1994; 32:39.
  84. Heckler FR. Current thoughts on extravasation injuries. Clin Plast Surg 1989; 16:557.
  85. Dorr RT. Antidotes to vesicant chemotherapy extravasations. Blood Rev 1990; 4:41.
  86. Uges JW, Vollaard AM, Wilms EB, Brouwer RE. Intrapleural extravasation of epirubicin, 5-fluouracil, and cyclophosphamide, treated with dexrazoxane. Int J Clin Oncol 2006; 11:467.
  87. Dührsen U, Heinrichs V, Beecken WD, et al. Local and systemic sequelae of mediastinal daunorubicin extravasation in a patient with acute myelomonocytic leukemia. Ann Oncol 1997; 8:1167.
  88. Anderson CM, Walters RS, Hortobagyi GN. Mediastinitis related to probable central vinblastine extravasation in a woman undergoing adjuvant chemotherapy for early breast cancer. Am J Clin Oncol 1996; 19:566.
  89. Rodier JM, Malbec L, Lauraine EP, et al. Mediastinal infusion of epirubicin and 5-fluorouracil. A complication of totally implantable central venous systems. Report of a case. J Cancer Res Clin Oncol 1996; 122:566.
  90. Haslik W, Hacker S, Felberbauer FX, et al. Port-a-Cath extravasation of vesicant cytotoxics: surgical options for a rare complication of cancer chemotherapy. Eur J Surg Oncol 2015; 41:378.
  91. Quintanar Verdúguez T, Blanco Jarava A, Martínez-Barbeito MB, et al. Mediastinal extravasation of doxorubicin. Clin Transl Oncol 2008; 10:128.