Extravasation of non-chemotherapeutic drugs

Last Friday, while I was on my internal medicine/neurology rotation, I had the opportunity to help manage extravasation from mannitol.  Therefore, I thought this week we could review the treatment of extravasation of non-chemotherapy drugs.

What is extravasation? Extravasation is defined as the leakage of intravenous drugs from the vein into the surrounding tissue.  Once extravasation has occurred, damage can continue for months and involve nerves, tendons and joints. If treatment is delayed, surgical debridement, skin grafting, and possibly amputation may be required.

Non-chemotherapy drugs are often not considered to be vesicants. However, these drugs can still extravasation. General risk factors for drugs that cause extravasation are1:

  • Intrinsically irritating to tissue (eg. nafcillin)
  • High osmolarity (eg. parenteral nutrition)
  • High pH (eg. phenytoin)


The table below provides treatment recommendations for extravasation caused by specific non-chemotherapy medications1.  It is important to mention treatments for extravasation are based on case reports in the literature; there are no randomized controlled trials (for obvious ethical reasons).


Drug/Drug Class


Extravasation Mechanism

Dextrose (≥ 10%)

*Hyaluronidase2, 3





Parenteral Nutrition

*Hyaluronidase2, 5;

Topical nitroglycerin2, 6



Warm compress7;

Topical nitroglycerin7, *Hyaluronidase8

High pH


  • Dobutamine
  • Dopamine
  • Epinephrine
  • Norepinephrine
  • Phenylephrine
  • Vasopressin

Phentolamine2, 9, 10;

Topical nitroglycerin11

Restriction of local blood flow

* The dose of hyaluronidase for adults for extravasation is 150 units/mL, 0.2 mL intradermally or subcutaneously at the edges surrounding the affected area.2, 3


Stay Warm!



  1. PL Detail-Document, Treatment for Extravasation of Non-Chemo Drugs. Pharmacist’s Letter/Prescriber’s Letter. December 2011.
  2. University of Illinois at Chicago. Drug extravasation: management summary and update. http://www.uic.edu/pharmacy/centers/drug_information_center/faq/-extravasation.php. (Accessed February 2, 2012).
  3. Wiegand R, Brown J. Hyaluronidase for the management of dextrose extravasation. Am J Emerg Med. 2010;81:257.e1-2.
  4. Kumar MM, Sprung J. The use of hyaluronidase to treat mannitol extravasation. Anesth Analg. 2003;97:1199-200.
  5. Gil ME, Mateu J. Treatment of extravasation from parenteral nutrition solution. Ann Pharmacother. 1998;32:51-5.
  6. Maddox TG. Adverse reactions to contrast material: recognition, prevention, and treatment. Am Fam Physician. 2002;66:1229-34.
  7. Edwards JJ, Bosek V. Extravasation injury of the upper extremity by intravenous phenytoin. Anesth Analg. 2002;94:672-3.
  8. Sokol DK, Dahlmann A, Dunn DW. Hyaluronidase treatment for intravenous phenytoin extravasation. J Child Neurol. 1998;13:246-7.
  9. The National Extravasation Information Service. www.extravasation.org.uk/. June 30, 2001. (Accessed February 2, 2012).
  10. Bey D, El-Chaar GM, Bierman F, Valderrama E. The use of phentolamine in the prevention of dopamine-induced tissue extravasation. J Crit Care. 1998;13:13-20.
  11. Denkler KA, Cohen BE. Reversal of dopamine extravasation injury with topical nitroglycerin ointment. Plast Reconstr Surg. 1989;84:811-3.


Courtney Shakowski, PharmD