Clinical Clue: (Intravenous Medication Extravasation Treatment)

Mechanism of Injury
Cannula Removal
Elevation and Splinting
Neutralizing Agent
Administration Guidelines
Hyaluronidase (Wyase®)


Allows osmotic agent to dilute and diffuse from site ,preventing compartmentalization, necrosis. 

Red margins "break up"

Reconstitute a 150 unit vial with 1 ml NS; take 0.1 ml of this solution and dilute with NS to yield 15 unit per ml; inject 0.2 ml SQ or intradermal around sites leading edge x 5. Change needle with each injection. Use 25-26G needle. Admin. Within 60 min. of infiltration.
10% Dextrose
Concentrated KCl
Contrast Dye
Intense Local Vasoconstriction
Warm or None
Phentolamine (Regetine®)


Reverses vasoconstriction IMMEDIATELY. Note return of color to skin. Skin "pinks up".

Admin. ASAP! Or within 12hrs of infiltration. Dilute 5 to10 mg in 10 ml NS. Inject directly into site multiple times. Change needle between injections. Use 25-26G Needle. 
Warm or None
Warm or None


Extravasation Management




EXTRAVASATION, the accidental leakage of intravenous fluid into the interstitial tissue, can result in severe injury with subsequent functional impairment and residual cosmetic defects. Surgical debridement and skin grafting may be required. Prolonged hospital stays and increased morbidity have been reported.


The POPULATION AT RISK includes infants and children who are too young to communicate the pain resulting from the pressure of extravasated fluid, the elderly, comatose patients, individuals under general anesthesia, and those receiving cardiac resuscitation. Other factors associated with the development of extravasation include the number of venipuncture attempts required to establish an intravenous line, the type intravenous cannula employed, the specific site of injection (ie, the dorsum of the hand and the dorsum of the foot are common sites of injury), certain disease states (ie, peripheral vascular disease, patients with elevated venous pressure), the use of infusion pumps, and a history of radiation to the injection site. The TREATMENT of extravasation injuries resulting from the infiltration of certain drugs and solutions involves the use of specific antidotes (see Table 1). The management of extravasation of chemotherapeutic agents has been published elsewhere (Ignoffo & Friedman, 1980; Larson, 1982; MacCara,1983; Faehnrich, 1984).

DRUGS that have been reported to cause damage upon infiltration, but for which no specific medical treatment could be found, are not discussed in this article.


Due to osmotic factors, solutions of 10% DEXTROSE (Yosowitz et al, 1975), concentrated infusions (ie, bolus vs continuous administration) of POTASSIUM (Upton et al, 1979; Brown et al, 1979) or CALCIUM (Yosowitz et al, 1975; Upton et al, 1979; Heckler & McCraw, 1976; Brown et al, 1979; Roberts, 1977), hypertonic PARENTERAL NUTRITION PREPARATIONS (Brown et al,1979) and RADIOCONTRAST MEDIA (Upton et al, 1979; Spigos, 1977) can cause tissue damage if INFILTRATION occurs.


Ischemic necrosis secondary to local vasoconstriction can result from extravasation of SYMPATHOMIMETIC AGENTS including DOBUTAMINE (Hoff et al, 1979), DOPAMINE (Upton et al, 1979;Brown et al, 1979; Greenlaw & Null, 1977), EPINEPHRINE (Upton et al, 1979; Gaze, 1978), METARAMINOL (Upton et al, 1979), and NOREPINEPHRINE (Weeks, 1966).The irritant properties of NAFCILLIN (Tilden et al, 1980; Zenk et al, 1981a; Moore & Terry, 1984) can be responsible for severe tissue injury following infiltration.


If extravasation occurs, the infusion should be immediately discontinued and, when available, a specific antidote administered.


CANNULA REMOVAL: Recommendations are equivocal. Guidelines exist for both immediate removal of the needle (Zenk, 1981b), as well as for its continued use as an access route to aspirate the extravasated solution before administering an antidote (Ignoffo & Friedman, 1980).

ELEVATION AND SPLINTING: Elevation of the affected area may provide adequate treatment for minor injuries and may preventserious complications (Upton et al, 1979; Brown et al, 1979). In addition, early and proper splinting of the injured area will facilitate resolution of swelling and prevent long-term damage and disability of the extremity.

COMPRESSES: Recommendations for application of heat or cold vary. Heat can increase drug distribution and absorption by inducing vasodilation. However, use of warm, moist compresses has resulted in maceration and subsequent tissue necrosis (Brown et al, 1979). Application of cold packs, through vasoconstriction and localization of the extravasated fluid, may be helpful if an antidote were to be locally injected; however,if no antidote is available, cold packs may result in more severe tissue damage at the site of infiltration (MacCara, 1983).

HYALURONIDASE (Wydase(R)): Hyaluronidase is an enzyme that temporarily decreases the viscosity of hyaluronic acid, the ground substance or intracellular cement of the tissues. Subcutaneous administration of hyaluronidase increases permeability into the tissues and facilitates absorption of the infiltrated solution by allowing diffusion of extravasated fluid over a larger area. This minimizes tissue injury through rapid

absorption and dilution in tissue fluids. The enzyme has an almost immediate onset of action and a 24 to 48 hour duration of effect on the "tissue cement." Allergic reactions, usually manifested as urticaria, occur rarely; otherwise, clinical reports emphasize minimal or lack of toxicity. The enzyme should not be injected into cancerous or acutely inflamed areas since there is a potential for disseminating infection or increasing the invasiveness or metastasis of neoplasms. The recommended concentration of hyaluronidase is prepared by either using 150 units/1 ml of the stabilized solution or reconstituting the vial of 150 units of lyophilized powder with 1 ml of 0.9% sodium chloride, followed by further dilation of 0.1 ml of either solution with saline to a final volume of 1 ml, resulting in a final concentration of 15 units per ml. After cleansing the infiltration site and surrounding area with povidone-iodine, approximately five 0.2-ml injections are administered subcutaneously or intradermally into the leading edge of the extravasation site, using a 25-gauge needle. The needle should be changed after each injection. A dose of 30 units has been used for severe, large infiltrates. Doses less than 15 units have been employed in preterm infants weighing less than one kg. Swelling is usually significantly decreased within 15 to 30 minutes following hyaluronidase administration. The enzyme must be used promptly, ie, within 60 minutes of the infiltration, since the potential for tissue damage increases with the duration of exposure to extravasated fluid. Hyaluronidase has been used successfully to prevent tissue injury due to infiltration of both nafcillin and the hyperosmotic agents listed in Table 1 (Hoff et al, 1979).

PHENTOLAMINE (Regitine(R)): Phentolamine, an alpha-adrenergic blocking agent, is used to treat extravasation of sympathomimetic agents. Competitive inhibition of the alpha effects of these drugs decreases local vasoconstriction and the resultant ischemia. The recommended dose of phentolamine is 5 to 10 mg, diluted in 10- to 15-ml sodium chloride 0.9%, injected with a fine hypodermic needle into the area of extravasation (defined by its cold, hard and pale appearance). Phentolamine should be administered within 12 hours of the infiltration; however, it is preferable to treat the injury as soon as possible (MacCara, 1983; Weeks, 1966; Zenk, 1981b; Prod Info,1981).

CORTICOSTEROIDS: The use of corticosteroids as anti-inflammatory agents in extravasation injuries is based upon recommendations for the treatment of infiltrations of cancer chemotherapeutic agents (MacCara, 1983). Hydrocortisone sodium succinate and dexamethasone sodium phosphate are most frequently utilized.

SILVER SULFADIAZINE (Silvadene(R)): Surgical evaluation and management should be considered when there is evidence of tissue necrosis. Application of silver sulfadiazine cream could prevent wound infections resulting from bacterial colonization of these areas (Brown et al, 1979; Zenk, 1981b).


Table 1


Extravasated Drug             Drug Treatment*             Reference

Hyperosmotic Solutions        Hyaluronidase                   Zenk, 1981b;

Calcium                              5 units/ml in normal saline   Zenk, 1981c

Dextrose 10%                     (5 injections of                   Zenk, 1981a;

Parenteral Nutrition               0.2 ml each)

Potassium                                                                   Zenk, 1981b;

Radiocontrast Media
Nafcillin                             Hyaluronidase  15 units/ml    Zenk, 1981c
                                                in normal saline
                                       (5 injections of 0.2 ml each)
Sympathomimetics              Phentolamine                    MacCara, 1983;

Dobutamine                         5 to 10 mg                        Zenk, 1981b

Dopamine                            in 10 to 15 ml

Epinephrine                         normal saline



*Silver sulfadiazine should be applied to areas of necrosis.


Prevention of extravasation is preferable to treatment of the resultant tissue damage. Recommendations include 1) appropriate dilution and rate of administration of drugs, 2) proper placement and location of intravenous sites (ie, avoidance of extremities with poor venous circulation), 3) proper splinting extremities with poor venous circulation), 3) proper splinting of the extremity while an intravenous cannula is in place to immobilize the extremity without constriction and prevent the cannula from tearing or eroding through the vessel, 4) careful and frequent monitoring of solutions administered by infusion pumps (at least hourly, and every few minutes during the infusion of irritating drugs) and 5) use of transparent dressings and clear tape to allow inspection of the injection site (MacCara, 1983; Upton et al, 1979; Brown et al, 1979; Zenk,1981b). However, when extravasation occurs, rapid administration of an appropriate antidote, elevation of the affected area, proper splinting of the extremity, use of silver sulfadiazine cream on areas of tissue necrosis, and surgical intervention as indicated, can minimize tissue injury.



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  3. Faehnrich J: Extravasation. NITA 1984; 7:49.

  5. Gaze NR: Tissue necrosis caused by commonly used intravenous infusions. Lancet 1978; 2:417.

  7. Greenlaw CW & Null LW: Dopamine-induced ischaemia. Lancet 1977; 2:555.

  9. Heckler FR & McCraw JB: Calcium-related cutaneous necrosis. Surg Forum 1976; 27:553.

  11. Hoff JV et al: Dermal necrosis from dobutamine. N Engl J Med 1979; 300:1280.

  13. Ignoffo RI & Friedman MA: Therapy of local toxicities caused by extravasation of cancer chemotherapeutic drugs.

  15. Canc Treat Rev 1980; 7:17. 8. Larson DL: Treatment of tissue extravasation by antitumor agents. Cancer 1982; 49:1796.

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  19. Moore RA & Terry BE: Nafcillin necrosis. NITA 1984; 7:61.

  21. Product Information: Dopamine hydrochloride (Intropin(R)). American Critical Care. January 1981.

  23. Roberts JR: Cutaneous and subcutaneous complications of calcium infusions. JACEP 1977; 6:16.

  25. Spigos DG et al: Skin necrosis following extravasation during peripheral phlebography. Radiology 1977; 123:605.

  27. Tilden SJ et al: Cutaneous necrosis associated with intravenous nafcillin therapy. Am J Dis Child 1980;134:1046.

  29. Upton J et al: Major extravasation injuries. Am J Surg 1979; 137:497.

  31. Weeks PM: Ischemia of the hand secondary to levarterenol bitartrate extravasation. JAMA 1966; 196:198.

  33. Yosowitz P et al: Peripheral intravenous infiltration necrosis. Ann Surg 1975; 182:553.

  35. Zenk KE: Management of intravenous extravasations. Infusion 1981b; 5:77.

  37. Zenk KE: Hyaluronidase: an antidote for intravenous extravasations. CSHP Voice 1981c; 8:66.

  39. Zenk KE et al: Nafcillin extravasation injury. Use of hyaluronidase as an antidote. Am J Dis Child 1981a;135:1113.


Original publication: 09/85

List of contributors:

David S Tatro, PharmD

Sharon D Ow-Wing, PharmD

DRUGDEX(R) Editorial Staff .