Extravasation
Extravasation refers to the leakage of a fluid out of its container. In the case of inflammation, it refers to the movement of white blood cells from the capillaries to the tissues surrounding it. In the case of malignant cancer metastasis it refers to cancer cells exiting the capillaries and entering organs. It is frequently used in medical contexts, either referring to urine, or to blood. In some languages (e.g. German), extravasation is called "paravasation".
The most frequent use in medicine, however, refers to extravasation of medicinal drugs during intravenous (IV) infusion.

# Overview of medicinal drug extravasation
Extravasation is the accidental administration of intravenously (IV) infused medicinal drugs into the surrounding tissue, either by leakage (e.g. because of brittle veins in very elderly patients), or direct exposure (e.g. because the needle has punctured the vein and the infusion goes directly into the arm tissue). Extravasation of medicinal drugs during intravenous therapy is a side-effect that can and must be avoided.
In mild cases, extravasation can cause pain, reddening, or irritation on the arm with the infusion needle. Severe damage may include tissue necrosis. In extreme cases, it even can lead to loss of an arm.

## Medicinal drugs
Medicinal drugs that cause only slight damage on the arm with the infusion needle if extravasated are called "irritants", and medicinal drugs that cause severe damage up to tissue necrosis if extravasated are called "vesicants".
Occurrence is possible with all IV drugs, but is a large problem with cytotoxic drugs for the treatment of cancer (i.e. during chemotherapy). The percentage of patients affected by extravasation may be as high as 10%. However, the actual percentage is unknown, since extravasation is often unnoticed and/or undocumented, especially if not severe.
In recent years, healthcare professionals are becoming more aware of this problem.    

# Treatments and Techniques
The best "treatment" of extravasation is prevention. While there is no real treatment per se, there are some techniques that can be applied in case of extravasation, though their efficacy is modest. If there is tissue necrosis, surgical reconstruction may be helpful. The following procedure may also be helpful if extravasation occurs:
- Stop infusion immediately. Put on sterile gloves.
- Replace infusion lead with a disposable syringe. While doing this, do not exert pressure on the extravasation area.
- Slowly aspirate back blood back from the arm, preferably with as much of the infusion solution as possible.
- Remove the original cannula or other IV access carefully from the arm.
- Elevate arm and rest in elevated position. If there are blisters on the arm, aspirate content of blisters with a new thin needle.
- If, for the extravasated medicinal drug, substance-specific measures apply, carry them out (e.g. topical cooling, DMSO, hyaluronidase or dexrazoxane may be appropriate).
- Recent clinical trials have shown that Savene (dexrazoxane for extravasation) is effective in preventing the progression of anthracycline extravasation into progressive tissue necrosis. In two open-label, single arm, phase II multicenter clinical trials, necrosis was prevented in 98% of the patients. Dexrazoxane for extravasation is the only registered antidote for extravasation of anthracyclines (daunorubicin, doxorubicin, epirubicin, idarubicin, etc.).

## Pain management and other measures
- Pain management is very important for the patient, as are full documentation and prevention of infection and superinfection. If there is superinfection, get an antibiogram and consult with an infectious diseases specialist. Of course, regular controls and aftercare are necessary.

## If the extravasated medicinal drug is a vesicant
- Do not flush the IV access
- No moist compresses, no alcohol compresses, no occlusive dressings
- Consult a physician with experience in the treatment of extravasation and a reconstructive surgeon early in the course of extravasation
- Such cases may necessitate skin grafting and intensive physiotherapy.

# Prevention of extravasation in hospitals
- Venipuncture and placement of the cannula (or other IV access) should be performed by experienced personnel, where available. Yet this is not always possible because of personnel resources. In this case, placement by experienced personnel for patients especially prone to extravasation (e.g. patients with hardly visible veins, very obese patients, very elderly patients, young children, etc.). In all other patients, avoid multiple venipunctures in the same area.
- Choose a large, intact vein with good blood flow for the venipuncture and placement of the cannula. Do not choose inadvertently "dislodgeable" veins (e.g. dorsum of hand or vicinity of joints) if an alternative vein is available.
- Use thin cannulas with high gauges. Check the position of the cannula by aspirating blood, as well as the patency of the vein by flushing with the carrier solution (e.g. 0.9% NaCl solution), before beginning the IV infusion.
- Observe infusion at least for the first 10 minutes and do the same every hour. Ask medical student/student nurse/patient/patient's family to do this for you if you do not have the time. Instruct them how to observe an infusion and to alert you as soon as possible if something seems to "go wrong".
- The IV infusion should be freely flowing. The arm with the infusion should not begin to swell (oedema), "get red" (erythema), "get hot" (local temperature increase), and the patient should not notice any irritation or pain on the arm. If this occurs, stop infusion immediately!
- The infusion should consist of a suitable carrier solution with an appropriately diluted medicinal/chemotherapy drug inside.
- After the IV infusion has finished, flush the vein "clean" with only the carrier solution.
- Finally, an excellently and very cleanly placed central line (= central venous catheter) is a huge advantage while infusing vesicant drugs.

# Examples of vesicant medicinal drugs

## Cytotoxic drugs
- Amsacrine
- Cisplatin (if > 0.4 mg/mL)
- Dactinomycin
- Daunorubicin
- Dexrazoxane
- Docetaxel
- Doxorubicin Hydrochloride

## Non-cytotoxic drugs
- Alcohol
- Aminophyllines
- Chlordiazepoxide
- Diazepam

# Notes
-  Sauerland C, Engelking C, Wickham R, Corbi D.  Vesicant extravasation part I: Mechanisms, pathogenesis, and nursing care to reduce risk. Oncol Nurs Forum. 2006 Nov 27;33(6):1134-41. Review.
-  Wickham R, Engelking C, Sauerland C, Corbi D. Vesicant extravasation part II: Evidence-based management and continuing controversies. Oncol Nurs Forum. 2006 Nov 27;33(6):1143-50. Review.
-  Goolsby TV, Lombardo FA. Extravasation of chemotherapeutic agents: prevention and treatment. Semin Oncol. 2006 Feb;33(1):139-43. Review.
-  Ener RA, Meglathery SB, Styler M. Extravasation of systemic hemato-oncological therapies. Ann Oncol. 2004 Jun;15(6):858-62. Review. Fulltext
-  Schrijvers DL. Extravasation: a dreaded complication of chemotherapy. Ann Oncol. 2003;14 Suppl 3:iii26-30. Review. Fulltext
-  For more information on substance-specific measures, see, for example, the textbook "Extravasation of cytotoxic agents" (Authors: I Mader et al., Springer Publishing House)
-  Mouridsen HT, Langer SW, Buter J, Eidtmann H, Rosti G, de Wit M, Knoblauch P, Rasmussen A, Dahlstrom K, Jensen PB, Giaccone G. Treatment of anthracycline extravasation with Savene (dexrazoxane): results from two prospective clinical multicentre studies. Ann Oncol. 2007 Mar;18(3):546-50.