The Art and Science of Infusion Nursing Sarah M. Martin, PharmD, MBA

Extravasation Management of Nonchemotherapeutic Medications ABSTRACT Many who think of vesicants think of chemotherapy and oncology patients. But not all vesicants are chemotherapy medications. This article reviews the factors that increase the risk of extravasation, the nonchemotherapeutic medications associated with extravasation injuries, and the recommended treatments. Key words: electrolytes, extravasation, hyaluronidase, infiltration, vesicant

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xtravasation is the inadvertent administration of a vesicant into the surrounding tissue instead of the intended vascular pathway.1-4 Infiltration is the inadvertent administration of a nonvesicant solution or medication into the tissue surrounding the intravenous (IV) catheter.4 A vesicant is an agent that has the potential to cause varying degrees of localized tissue damage when leaked or inadvertently administered into the tissue.4-8 The key difference between an extravasation and an infiltration is whether the solution or medication that leaked into the surrounding tissue is considered a vesicant. Generally speaking, most who think of vesicants think of chemotherapy and oncology patients. But not all vesicants are chemotherapy medications (Table 1). Vesicants can cause damage by various mechanisms.11 Causing direct cellular injury or having inherently caustic properties are most commonly associated with chemotherapy agents. Nonchemotherapeutic medications may cause damage by having a nonphysiological pH (less than 5.0 or greater than 9.0), being highly ionized, being Author Affiliations: St John Medical Center, Tulsa, Oklahoma, and Rogers State University, Claremore, Oklahoma. Sarah M. Martin, PharmD, MBA, is a clinical pharmacist at St John Medical Center in Tulsa, Oklahoma, and an adjunct faculty member in the Health Sciences Department at Rogers State University in Claremore, Oklahoma. The author of this article has no conflicts of interest to disclose. Corresponding Author: Sarah M. Martin, PharmD, MBA ([email protected]). DOI: 10.1097/NAN.0000000000000010

hyperosmolar, or causing vasoconstriction and subsequent tissue ischemia.11,14 The risk factors associated with an increase in extravasation are not unique to oncology patients. They can be divided into device-related, patient-related, and clinician-related risk factors (Table 2). It would be ideal to decrease the risk of an extravasation and prevent it from occurring, but that is not always possible. The damage associated with an extravasated medication can range from mild discomfort, pain, and swelling to tissue necrosis.1,2,4,5,7-9 The severity of damage the vesicant causes is in part determined by the amount and concentration of the medication extravasated, the location of the extravasation, how quickly the health care worker intervenes, and the type of vesicant extravasated.1,6,8

REVIEW OF TREATMENTS Various treatment modalities have been used after an extravasation has occurred. Although no single treatment has been found curative, a compilation of modalities has been found beneficial. The type of treatment is dependent on the vesicant that has caused the damage. The following is a review of each treatment individually. Nonpharmaceutical Treatments Elevation Elevation of the extremity where the extravasation has occurred can help minimize swelling and aid in the management of both infiltration and extravasation.2,3,5,9,11,15 Elevation decreases the hydrostatic pressure in the capillaries and allows fluid to dissipate.15 Movement of the area should be encouraged in order to help prevent the adhesion of damaged areas to the underlying tissues.9 Typically, elevation is recommended for the first 48 hours after the extravasation.2 Temperature Interventions Cold packs not only relieve some of the pain associated with the extravasation by acting as a nerve conduction

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TABLE 1

TABLE 2

Nonchemotherapeutic Medications Implicated in Extravasation Injuries

Factors Associated With an Increased Risk of Extravasation

3-5,9-13

Anti-infectives

1-6,8-11

Device related Use of metal “butterfly” needle Lack of blood return before infusion

Acyclovir

Inadequately secured needle or catheter

Amikacin Amphotericin B Dicloxacillin

Placement in an undesirable location Antecubital fossa Dorsum of hand

Nafcillin

Wrist

Oxacillin

Areas of flexion/movement-prone areas

Vancomycin Electrolyte solutions Calcium chloride Calcium gluconate Parenteral nutrition Potassium chloride Sodium bicarbonate Sodium chloride > 0.9% Vasopressors

Patient related Age (very young or elderly) Hard or sclerosed veins Small veins Fragile veins Impaired communication or altered sensory perception Sedation/somnolence Impaired cognition/altered mental status Unconscious/use of general anesthetics/comatose

Dobutamine

Patient movement (vomiting, coughing, stretching, seizures)

Dopamine

Clinician related

Epinephrine

Lack of IV insertion skills

Norepinephrine Miscellaneous

Probing during IV insertion Interruptions/distractions during administration

Aminophylline

Abbreviation: IV, intravenous.

Chlordiazepoxide Contrast media Dextrose ≥ 10% Diazepam Digoxin Doxapram Intralipids Mannitol Phenytoin Promethazine Urea

block6 but also prevent the spread of the damaging substance to adjacent tissues by causing vasoconstriction of the blood vessels.4,6,9,12 Cold packs should be applied for 15 to 20 minutes at least 4 times a day for the first 24 to 48 hours after the extravasation has occurred.5,8,9

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Care should be taken to not cause further damage of the area by inducing frostbite. Alternatively, warm packs increase the dispersion and dilution of the extravasated fluid by causing vasodilatation, increasing blood flow to the area and promoting its reabsorption.4,9,12,16,17 This will decrease the swelling in the area and thus decrease some of the pain associated with the extravasation.9 Moist heat is not recommended because it can cause maceration and may further damage already compromised skin. Warm packs should be applied for 15 to 20 minutes at least 4 times a day for the first 24 to 48 hours after the extravasation has occurred.2,5,8,9,16 In determining which temperature pack to use on each patient, a few factors should be considered. If the goal is to maintain the extravasated material in a localized area,4,6,9,12 cold packs should be chosen. If, however, the goal is to dissipate the extravasated material

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and enhance the reabsorption either alone or in conjunction with a pharmacological treatment,4,9,12,16,17 warm packs are preferred. Lastly, if the medication or solution that has escaped the vasculature is not known to be a vesicant, the patient preference for cold or warm packs should be considered. Pharmacological Treatments Hyaluronidase Hyaluronidase is an enzyme that breaks down hyaluronic acid.4-6,8,9,12,15 Hyaluronic acid is a major part of the skin and connective tissues. By breaking down the hyaluronic acid and temporarily decreasing the viscosity of the extracellular matrix of the skin, it promotes diffusion of the extravasated fluid and allows for enhanced absorption.4-6,8,9,12 Hyaluronidase is available as a 150-unit/mL concentration and should be injected within 60 minutes of the extravasation. The recommended

Figure 1 Injection pattern recommendations for hyaluronidase administration. Illustration by author.

injection method is to use 5 separate injections of 30 units (0.2 mL) per injection in a clockwise manner around the leading edge of the extravasation site using a 25-gauge or smaller needle (Figure 1).2,6,8,12 Swelling is usually significantly decreased within 15 to 30 minutes after administration. Some case studies have used as much as 1500 units,6,8,9 whereas others have added

Figure 2 Sample of initial extravasation/infiltration treatment strategy. Adapted and used with permission. © Thomas Land Publishers, Inc. www.hpjwallcharts.com.

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small amounts of 1% procaine or lidocaine to the solution to decrease pain associated with the injections.18 Adverse reactions, such as injection site reactions, bruising, allergic reactions, and urticaria, are possible with hyaluronidase.19,20 Additionally, reactions associated with the rapid absorption of the medication extravasated are possible, particularly with high concentrations or large volumes of extravasate. It is not uncommon in the literature to find hyaluronidase used in combination with cold packs.9,13-15 The use of an antidote to promote the diffusion of fluid (hyaluronidase) combined with an intervention that prevents the spread of fluid (cold packs) seems counterproductive, however. References to this combination are likely due to many of the recommendations regarding extravasations of chemotherapy drugs. These drugs are directly damaging to cells, and it is essential to limit exposure to these drugs while reabsorption occurs. With nonchemotherapeutic medications, however, this need is limited or nonexistent, and therefore, hyaluronidase should be used in combination with warm packs when temperature therapy is also used.

TABLE 3

Items to Be Documented After Extravasation Event Occurs 1-2,6,8,9,11

General information Patient’s name and phone number Date and time of event Clinical area where event occurred Names and signatures of nurses administering the medication Drug and infusion information Drug name, dose, volume, and concentration Site of venous access (peripheral, central, VAD, etc) Needle size and type Any difficulty in venipuncture Amount of drug remaining in bag/syringe

Phentolamine Phentolamine competitively blocks alpha-adrenergic receptors, resulting in the relaxation of vascular smooth muscle and subsequent vasodilation.19,21 Generally used for extravasations that cause damage through vasoconstriction, vasodilation allows blood flow to return and decreases the amount of ischemic injury.4 This treatment is best done immediately after an extravasation, but it should be administered within 12 hours at the latest. The injection should be prepared by diluting 5 to 10 mg of phentolamine in 10 mL of normal saline.4,19,21,22 The resulting admixture should be injected subcutaneously around the area after catheter removal. Normal skin color should return to the blanched area within 1 hour. Injection site pain, nausea, vomiting, and pruritus may occur.19,21 Because phentolamine is a vasodilator, other adverse effects, such as hypotension, orthostatic hypotension, tachycardia, weakness, flushing, and nasal congestion, are possible.19,21 Conversely, if a large amount of fluid is extravasated and then rapidly reabsorbed with phentolamine treatment, the adverse effects of hypertension, dysrhythmia, headache, and paresthesias may occur.19,21 The availability of phentolamine has not been consistent because of drug shortages, and alternative treatments have been needed. Some references have suggested using terbutaline 1 mg mixed in 10 mL of normal saline and injected subcutaneously around the area after catheter removal.23 A 1- to 2-inch ribbon of nitroglycerin ointment spread over the affected area has also been used.12 Similar to phentolamine, both of these can lead to hypotension, dysrhythmias, and tachycardia.19

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Amount of drug aspirated Drugs (in order administered) Appearance of infusion site (photograph in color if possible) Patient’s symptoms Patient’s comments Interventions Physical measures used to prevent further extravasation Process for physician notification Name, dose, and route of any antidotes Describe use of warm or cold compresses Note surgical or other consults requested Method of elevation Patient education Give verbal and written instructions Ensure the patient has a follow-up appointment Describe the care of the site (elevate, compresses, do not immerse, etc) Instruct patient to call provider for any of the following: Increased pain Skin color change Increased edema or swelling Stiffness in the extremity Skin breakdown Fever Any additional questions Abbreviation: VAD, venous access device.

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Estimated amount of extravasated drug

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MANAGEMENT OF EXTRAVASATION As stated previously, the best treatment for extravasation is prevention. When an extravasation does occur, however, it should be treated promptly. But, because of the lack of available recommendations and guidelines, there is often inconsistency and confusion regarding which therapies to use. This uncertainty can significantly delay appropriate treatment and potentially worsen the extent of the patient’s injuries. To ensure timely and efficient treatments, it is recommended that each facility develop its own set of general and drug-specific policies and procedures (Figure 2).8,9,12,16 Policies regarding documentation, physician notification, and patient education requirements will also aid in the process and improve consistency between events. Documentation should be completed immediately after the extravasation protocol is completed and placed in the patient’s permanent medical record. Recommendations for items that should be included in the documentation can be found in Table 3. The recommendations that follow are based on case reports and theoretical principles that attempt to reduce the extent of tissue injury once extravasation has occurred. Treatment of extravasation injury with certain techniques is controversial, and there are no welldesigned, controlled clinical trials proving efficacy or safety. Therapy should be based on individual cases and clinical judgment. REFERENCES 1. Sauerland C, Engelking C, Wickham R, et al. Vesicant extravasation part 1: mechanisms, pathogenesis and nursing care to reduce risk. Oncol Nurs Forum. 2006;33(6):1134-1141. 2. Mullin S, Beckwith MC, Tyler LS. Prevention and management of antineoplastic extravasation injury. Hosp Pharm. 2000;35: 57-74. 3. Viale PH. Chemotherapy and cutaneous toxicities: implications for oncology nurses. Semin Oncol Nurs. 2006;22(3):144-151. 4. Hadaway L. Infiltration and extravasation: preventing a complication of IV catheterization. Am J Nurs. 2007;107(8):64-72.

5. Froiland K. Extravasation injuries: implications for WOC nursing. J Wound Ostomy Continence Nurs. 2007;34(3):299-302. 6. Schulmeister L. Extravasation management: clinical update. Semin Oncol Nurs. 2011;27(1):82-90. 7. Gorski LA. Standard 54: infiltration. J Infus Nurs. 2007;30(6): 330-331. 8. Wengstrom Y, Margulies A. European Oncology Nursing Society extravasation guidelines. Eur J Oncol Nurs. 2008;12:357-361. 9. Dougherty L. Extravasation: prevention, recognition and management. Nurs Stand. 2010;24(52):48-55. 10. Steinmann G, Charpentier C, O’Neill TM, et al. Liposuction and extravasation injuries in ICU. Br J Anaesth. 2005;95(3):355-357. 11. Khan MS, Holmes JD. Reducing the morbidity from extravasation injuries. Ann Plast Surg. 2002;48:628-632. 12. Schulmeister L. Readers share comments and questions about extravasation management. Oncol Nurs Forum. 2007;34(2): 275-280. 13. Hurst S, McMillan M. Innovation solutions in critical care units: extravasation guidelines. Dimens Crit Care Nurs. 2004;23(2):125128. 14. Roszell S, Jones C. Intravenous administration issues: a comparison of intravenous insertions and complications in vancomycin versus other antibiotics. J Infus Nurs. 2010;33(3):112-118. 15. Schaverien MV, Evison D, McCulley SJ. Management of large volume CT contrast medium extravasation injury: technical refinement and literature review. J Plast Reconstr Aesthet Surg. 2008;61:562-565. 16. Wickham R, Engelking C, Sauerland C, Corbi D. Vesicant extravasation part II: evidence-based management and continuing controversies. Oncol Nurs Forum. 2006;33(6):1143-1150. 17. Schrijvers DL. Extravasation: a dreaded complication of chemotherapy. Ann Oncol. 2003;14(suppl 3):iii26-iii30. 18. Kumar MM, Spring J. The use of hyaluronidase to treat mannitol extravasation. Anesth Analg. 2003;97:1199. 19. Lexi-Comp [database online]. Hudson, OH: Lexi-Comp, Inc.; 2012. Accessed March 2013. 20. Hyaluronidase. In: DRUGDEX System [database online]. Greenwood Village, CO: Thomson Reuters; 2012. Accessed March 2013. 21. Phentolamine. In: DRUGDEX System [database online]. Greenwood Village, CO: Thomson Reuters; 2012. Accessed March 2013. 22. Thigpen JL. Peripheral intravenous extravasation: nursing procedure for initial treatment. Neonatal Netw. 2007;26(6):379-384. Accessed March 2013. 23. Stier PA, Bogner MP, Webster K, et al. Use of subcutaneous terbutaline to reverse peripheral ischemia. Am J Emerg Med. 1999;17(1):91-94. Accessed March 2013.

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Extravasation management of nonchemotherapeutic medications.

Many who think of vesicants think of chemotherapy and oncology patients. But not all vesicants are chemotherapy medications. This article reviews the ...
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