Case Report

Hyaluronidase for the management of dextrose extravasation

Abstract

Intravenous catheter malfunction causing extravasation is a common occurrence in the emergency department (ED). A 17-year-old girl who had a syncopal episode was given an ampule of dextrose 50% water into her antecubital region by emergency medical services. During her evaluation at the ED, she developed erythema and swelling in the antecubital region where the dextrose was given and extravasation was suspected. Most extravasations have relatively minor sequelae, but once an extravasation has occurred, damage can continue for months and involve nerves, tendons, and joints. If treatment is delayed, surgical debridement, Skin grafting, and even amputation have been reported in literature. Hyaluronidase is a parenteral protein enzyme traditionally derived from bovine testicular tissue. Hyalur- onidase is used as adjunct therapy to increase the absorption and dispersion of other injected drugs. The drug has also been used as an adjunct to nonpharmacologic management of extravasation of selected antineoplastic agents and other irritants. Although hyaluronidase does not have a Food and Drug Administration indication for dextrose extravasation, literature has shown improved outcomes for other hyper- osmolar substances. Hyaluronidase was used by injecting

0.2 mL (150 U/1 mL) with a 25-gauge needle at 5 different sites along the leading edge of erythema. The patient’s symptoms improved, and there were no complications noted at follow-up at 48 hours and at 6 months. The use of hyaluronidase should be considered for the management of dextrose extravasations and other extravasations.

Intravenous administration of fluids and medications carries with it the risk of tissue damage after catheter malfunction. Extravasation, or infiltration, occurs when fluids or medications penetrate into the tissues surrounding an intravenous site after damage to the vessel endothelium. Although the literature varies, the incidence of extravasations is believed to range from 10% to 30% [1-3]. Most extravasations have relatively minor sequelae, but once an extravasation has occurred, damage can continue for months and involve nerves, tendons, and joints. If treatment is delayed, surgical debridement, skin grafting, and even

amputation have been reported in literature [1-4]. We report the use of hyaluronidase in the setting of dextrose infiltration. A 17-year-old girl was brought to the emergency depart- ment (ED) after a syncopal episode while at work. Emergency medical services evaluated the patient. They documented hypoglycemia and administered 1 ampule of D50W intrave- nously in her right antecubital fossa. During transport to

the ED, she had reduction in her sense of light-headedness. In the ED, she was awake and alert without complaints,

with the exception of pain in her right arm. Her initial vitals signs were temperature of 98.7 (?F), heart rate of 88 (beat/min), respiratory rate of 16 (breath/min), and oxygen saturation of 99% on room air. Positive findings were limited to her arm. There was significant erythema and soft tissue swelling in the antecubital fossa and proximal arm. The patient’s discomfort abated only after 2 doses of morphine were administered intravenously through an infusion in the contralateral arm.

The cause for the patient’s syncope was explored. She was provided the following management for a dextrose extravasation. The affected arm was elevated, and cold compresses were applied. After discussing the risks and benefits and possible alternatives for treatment with the girl’s parents, the parents agreed to proceed with the use of hyaluronidase, a treatment for dextrose extravasation that was not approved by the Food and Drug Administration. A total of 150 U (1 mL) of hyaluronidase was injected subcutaneously in the antecubital region. Five injections of

0.2 mL were infused with a 25-gauge needle in sites equally spaced around the edges of the extravasation site. Within 30 minutes, the patient’s pain lessened, erythema abated, and soft tissue swelling was noted to improve. The patient was monitored for 40 minutes after the administration. She was advised to maintain the arm in an elevated position. A follow-up appointment in 48 hours was arranged so that the patient could be reassessed for both her syncopal episode and for a wound check. At follow-up, the patient was well. She had no recognized adverse reaction at the extravasation site. A follow-up call at 6 months reconfirmed that she had no further syncopal episodes and had no long-term sequelae with her arm.

All substances given through the intravenous route can cause tissue injury after extravasation. Certain substances are associated with a greater risk of tissue necrosis after extravasation. Chemotherapeutics cause local tissue injury

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through direct cellular toxicity. Hyperosmolar substances, such as parenteral nutrition solutions, mannitol, and dextrose, cause tissue damage by altering osmotic pressure. The increased osmotic pressure causes a shift of water from the intracellular to extracellular space. This increased fluid load leads to Increased tissue pressure and hypoxia.

Hyaluronidase is a parenteral protein enzyme traditionally derived from bovine testicular tissue. Newer products are prepared from purified ovine testicular tissue. Most recently, a recombinant human preparation has become available. Hyaluronidase is used as adjunct therapy to increase the absorption and dispersion of other injected drugs. The drug has also been used for hypodermoclysis, as an adjunct in subcutaneous urography for improving resorption of radio- paque agents, and as an adjunct to nonpharmacologic management of extravasation of selected antineoplastic agents and other irritants [5]. Hyaluronidase breaks down hyaluronic acid in connective tissue resulting in increased permeability and enhanced diffusion of subcutaneously administered agents. Hyaluronidase hydrolyzes hyaluronic acid by splitting the glucosaminidic bond between C1 of the glucosamine moiety and C4 of glucuronic acid. This temporarily decreases the viscosity of the cellular cement and promotes diffusion of injected fluids or of localized transudates or exudates, thus facilitating their absorption. The rate of diffusion is proportionate to the amount of enzyme administered, and the extent is proportionate to the volume of solution [5].

Hyaluronidase is not Food and Drug Administration approved for glucose extravasation. However, it has been reported to improve outcomes with various extravasations from several hyperosmolar substances [6,7]. The dosing for hyaluronidase in extravasation injuries varies from adults to children and also with the amount of extravasated material. Total doses of 150 to 900 U have been used in adults. The total dose is divided, and the injected material is placed subcutaneously or intradermally between 5 and 10 sites

along the leading edge of the extravasation. For children and infants, total doses of 15 to 150 U have been used. The total dose is injected subcutaneously or intradermally in 4 sites along the leading edge of the extravasation [5,8].

Hyaluronidase has shown benefit for extravasations of various hyperosmolar agents. Its use has not been empha- sized in the emergency medicine literature. Although it cannot be said for certain that the treatment with hyalur- onidase in this particular patient contributed to a positive outcome, it is worth including this potential positive benefit in the emergency medicine literature.

Robb Wiegand MD James Brown MD

Department of Emergency Medicine

Wright State University Boonshoft School of Medicine Dayton, OH 45429, USA

E-mail address: [email protected] doi:10.1016/j.ajem.2009.06.010

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