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Continuing Nursing Education (CNE) CreditA total of 3.1 contact hours may be earned as CNE credit for reading the articles in this issue identified as CNE and for completing an online post-test and evaluation. To be successful the learner must obtain a grade of at least 80% on the test.

DisclosureThe author has no relevant financial interest or affiliations with any commercial interests related to the subjects discussed within this article. No commercial support or sponsorship was provided for this educational activity.

Accepted for publication June 2012.

This ArTicle reviews The

history of hyaluronidase, contributing factors that predispose neonates to peripheral intravenous (iv) infiltration; terms associated with inf iltration and extravasa-tion; the mechanism of action of hyaluronidase; staging and treat-ment of extravasated tissue, along with the economic cost and liability associated with iv infiltrates.

The insertion of an iv catheter is the most common invasive procedure in neonatal intensive care unit (NicU).1 intravenous administration of fluids and medications is a necessary treatment for many newborns in the NicU, yet it is not without potential adverse effects. The fragile skin of the neonate places them at greater risk for alterations in skin integrity.2 inadvertent catheter dislodgement outside of the vein with subsequent leakage of fluid into the surrounding tissue can cause varying degrees of local irritation; and in the most severe cases, can cause tissue necrosis, and limb loss. it is estimated that up to 78 percent of ivs become infil-trated, and extravasation occurs in approximately 11 percent of all NicU patients, with a higher prevalence of extravasa-tion injury resulting in skin necrosis in infants with a gesta-tional age of 26 weeks or less.3–5 subcutaneous injections of hyaluronidase in the tissue surrounding extravasation have been shown to decrease tissue damage and necrosis.1

HISTORICAL REVIEWMeyer and Palmer first discovered hyaluronic acid in bovine

vitreous humor in 1934.6 later, Karl Meyer introduced the term hyaluronidase, which included a group of enzymes that was capable of degrading hyaluronic acid.7 important to the discussion of hyaluronic acid and hyaluronidase is the understanding that they are not one in the same, and in fact, have opposing actions. Girish and Kemparaju who wrote that hyaluronic acid is the “magic glue and hyaluroni-dase is its eraser” perhaps best describe the difference.7 hyaluronic acid is readily available in many human tissues but most abundant in soft connective tissue with particu-larly high concentrations found in the umbilical cord, skin, synovial fluid, and vitreous humor. hyaluronic acid plays a role in many biomedical applications because of its regenera-tive ability, including treatment for osteoarthritis, cataract surgery, embryo implantation, and in cosmetic procedures, to name a few.

in the 1930s, Duran-reynals discovered the “spreading factor” of hyaluronidase described as the depolymerisation of hyaluronic acid, the benefit of which aids in dispersion and reduction of edema. research into the “spreading effect” dis-covered by Duran-reynals and advanced by chain and Duthie in the 1940s, led to the use of hyaluronidase in conjunction

with local anesthetic agents to increase diffusion in spreading the anesthetic action of agents.8 Over the next several decades, researchers found hyaluronidase was effective in treating a variety of conditions ranging from trau-matic swelling in oral dentistry

to the correction of hyaluronic acid–based fillers in cosmetic dermatology.9,10 its use as an antidote was first proposed in 1976.11 in the 1980s, the study of hyaluronidase for the treatment of nafcillin-induced deep tissue necrosis helped advance the use of hyaluronidase as an antidote for iv infil-tration.12 in studies using the skin of immature pigs (which resembles human skin), injection of hyaluronidase was found to decrease skin necrosis and overall morbidity associated with iv extravasation injuries.13 Additional animal model studies showed significant reduction of areas of skin loss and ulceration when hyaluronidase was given less than one hour from the time extravasation occurred.3 current therapy for the treatment of iv infiltrates varies among institutions, ranging from conservative to aggressive. in the most conser-vative approach, the wound is exposed to air and occlusive dressings with hydrogels and nonocclusive saline dressings are used. in a more aggressive approach, administrations of antidotes such as hyaluronidase are used. Treatment is also dependent on factors such as the stage of extravasation, type of infiltrating solution, and availability of antidotes.1

RISK FACTORS FOR IV COMPLICATIONS REQUIRING THE USE OF HYALURONIDASE

Neonates can neither report pain nor advocate for them-selves, thus recognizing those at particularly high risk, along with vigilance in monitoring iv sites is vital. in addition to gestational age and the fragile nature of a neonate’s skin as risk factors, a number of factors predispose newborns to adverse outcomes of iv therapy (Table 1).

INFILTRATION VERSUS EXTRAVASATIONThe terms infiltration and extravasation are often used

interchangeably to describe displacement of an iv catheter and subsequent collection of fluid around the peripheral site.

Hyaluronidase for Extravasation Management

Michele J. Beaulieu, DNP, ARNP, NNP-BC

Pointers in Practical Pharmacology