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`(cid:39)(cid:9)(cid:10)(cid:6)(cid:12)(cid:13)(cid:10)(cid:7)(cid:2) (cid:47)(cid:10)(cid:24)(cid:2)(cid:18)(cid:53)(cid:5)(cid:10)(cid:24)
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`(cid:42)(cid:4)(cid:58)(cid:13)(cid:10)(cid:7)(cid:2)(cid:4) (cid:32)(cid:10)(cid:7)(cid:9)(cid:18)(cid:9)(cid:24)(cid:33) (cid:43)(cid:8)(cid:15)(cid:6)(cid:5)(cid:10)(cid:24) (cid:46)(cid:2)(cid:6)(cid:9)(cid:8)(cid:15)(cid:7)(cid:2)(cid:6)
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`(cid:41)(cid:14)(cid:2) (cid:39)(cid:60)(cid:47) (cid:39)(cid:9)(cid:10)(cid:6)(cid:8)(cid:18)(cid:12)(cid:5)(cid:10)(cid:24) (cid:55)(cid:15)(cid:9)(cid:8)(cid:16)(cid:11) (cid:40)(cid:10)(cid:7)(cid:23)
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`(cid:27)(cid:8)(cid:28) (cid:37)(cid:54)(cid:57)(cid:59)(cid:40)(cid:39)(cid:42)(cid:41)(cid:40)(cid:32)(cid:43)(cid:1) (cid:29)(cid:30)(cid:28) (cid:39)(cid:40)(cid:41)(cid:42)(cid:41)(cid:40)(cid:32)(cid:43)(cid:1)
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`(cid:31)(cid:31) (cid:37)(cid:54)(cid:57)(cid:59)(cid:40)(cid:39)(cid:42)(cid:41)(cid:40)(cid:32)(cid:43)(cid:1) (cid:29)(cid:27)(cid:32) (cid:39)(cid:40)(cid:41)(cid:42)(cid:41)(cid:40)(cid:32)(cid:43)(cid:1)
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`(cid:1)(cid:47)(cid:47) (cid:37)(cid:46)(cid:32)(cid:50)(cid:40)(cid:59)(cid:47)
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`(cid:50)(cid:13)(cid:34)(cid:5)(cid:18)(cid:33) (cid:10)(cid:2)(cid:2)(cid:4)(cid:6) (cid:17)(cid:9)(cid:15) (cid:10)(cid:8)(cid:15)(cid:6)(cid:5)(cid:10)(cid:24) (cid:7)(cid:13)(cid:15)(cid:2) (cid:13)(cid:12) (cid:12)(cid:14)(cid:2) (cid:2)(cid:10)(cid:4) (cid:9)(cid:17) (cid:18)(cid:5)(cid:17)(cid:2) (cid:5)(cid:10) (cid:12)(cid:14)(cid:2) (cid:13)(cid:7)(cid:8)(cid:12)(cid:2) (cid:7)(cid:13)(cid:15)(cid:2) (cid:6)(cid:2)(cid:12)(cid:12)(cid:5)(cid:10)(cid:24) (cid:51)(cid:5)(cid:2)(cid:22) (cid:16)(cid:15)(cid:9)(cid:52)(cid:2)(cid:7)(cid:12)
`
`(cid:47)(cid:10)(cid:14)(cid:13)(cid:10)(cid:7)(cid:5)(cid:10)(cid:24) (cid:39)(cid:9)(cid:34)(cid:34)(cid:8)(cid:10)(cid:5)(cid:7)(cid:13)(cid:12)(cid:5)(cid:9)(cid:10) (cid:1)(cid:53)(cid:5)(cid:18)(cid:18)(cid:6) (cid:9)(cid:17) (cid:40)(cid:39)(cid:54) (cid:43)(cid:8)(cid:15)(cid:6)(cid:2)(cid:6) (cid:42)(cid:15)(cid:9)(cid:8)(cid:10)(cid:4) (cid:48)(cid:5)(cid:6)(cid:7)(cid:8)(cid:6)(cid:6)(cid:5)(cid:9)(cid:10)(cid:6) (cid:9)(cid:17) (cid:37)(cid:15)(cid:9)(cid:24)(cid:10)(cid:9)(cid:6)(cid:5)(cid:6)(cid:11) (cid:13)(cid:10)(cid:4) (cid:55)(cid:9)(cid:13)(cid:18)(cid:6) (cid:9)(cid:17) (cid:39)(cid:13)(cid:15)(cid:2)
`
`(cid:48)(cid:2)(cid:7)(cid:5)(cid:6)(cid:5)(cid:9)(cid:10)(cid:56)(cid:38)(cid:13)(cid:53)(cid:5)(cid:10)(cid:24) (cid:51)(cid:5)(cid:2)(cid:22) (cid:16)(cid:15)(cid:9)(cid:52)(cid:2)(cid:7)(cid:12)
`
`(cid:42)(cid:18)(cid:18) (cid:7)(cid:9)(cid:10)(cid:12)(cid:2)(cid:10)(cid:12) (cid:17)(cid:9)(cid:18)(cid:18)(cid:9)(cid:22)(cid:5)(cid:10)(cid:24) (cid:12)(cid:14)(cid:5)(cid:6) (cid:16)(cid:13)(cid:24)(cid:2) (cid:22)(cid:13)(cid:6) (cid:8)(cid:16)(cid:18)(cid:9)(cid:13)(cid:4)(cid:2)(cid:4) (cid:19)(cid:33) (cid:48)(cid:2)(cid:19)(cid:9)(cid:15)(cid:13)(cid:14) (cid:57)(cid:9)(cid:33)(cid:18)(cid:2) (cid:9)(cid:10) (cid:31)(cid:28) (cid:1)(cid:2)(cid:16)(cid:12)(cid:2)(cid:34)(cid:19)(cid:2)(cid:15) (cid:45)(cid:31)(cid:25)(cid:26)(cid:23)
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`(cid:41)(cid:14)(cid:2) (cid:8)(cid:6)(cid:2)(cid:15) (cid:14)(cid:13)(cid:6) (cid:15)(cid:2)(cid:61)(cid:8)(cid:2)(cid:6)(cid:12)(cid:2)(cid:4) (cid:2)(cid:10)(cid:14)(cid:13)(cid:10)(cid:7)(cid:2)(cid:34)(cid:2)(cid:10)(cid:12) (cid:9)(cid:17) (cid:12)(cid:14)(cid:2) (cid:4)(cid:9)(cid:22)(cid:10)(cid:18)(cid:9)(cid:13)(cid:4)(cid:2)(cid:4) (cid:17)(cid:5)(cid:18)(cid:2)(cid:23)
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`Vesicant extravasation: myths and realities.
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`Vesicant Extravasation: Myths and Realities
`
`Deborah McCatirey Boyle and Constance Engelking
`
`petent performance as a certified oncology nurse (Ropka,
`Norback, Rosenfcld,.Millcr, & Nielsen, 1992).
`Unfortunately, prompt recognition and effective man-
`agement of extravasation injury are hampered by unan-
`SWEl'eCl questions about the nature of vesicant extravasa-
`tion, lack of scientific data upon Which to base treatment
`
`Deborah McCafii‘ey Boyle, RN, MSN, OCN, is an oncology
`clinical run-s6: specialist or The Cancer- Center at Fairfax Hos-
`pital in Falls Church, VA. Collisions-e Eugelkiug, RN, MS, OCN,
`is on oncology clinical muse specialist or the Manchester
`County Medical Center in Valhalla, NY. Sections ofrltis article
`previously were published in D. McConrl-ey & C. Eugellciug.
`(l 9901. Ten fallacies associated with the nature and manage-
`ment of chemotherapy exrrovosotlou. Progressions: Develop-
`ments in Ostomy and Wound Management, 2(4), 3—10. (Sub-
`mitted December, 1993. Acceptedfor publication August 26,
`I994. ) (Mention of specific products and opinions related to
`those products do not indicate or imply endorsement by the On-
`cology Nursing Forum or the Oncology Nursing Society.)
`
`sient swelling, erythema, and mild to moderate temporary
`pain. Applications of heat or cold and elevation of the af-
`fected extremity are the most common clinical interven-
`tions for nonvesicant infiltrations and usually provide
`adequate relief from symptoms (Dorr & Alberts, 1985;
`Dorr, Alberta, 8: Stone, 1985; Hastings—Tolsma et al.,
`1993). In contrast, as a result of their chemical composi-
`tion and mechanism of action, vesicant extravasations can
`result in progressive and severe tissue destruction, pro-
`duce significant pain, and ultimately interfere with the
`affected extremity’s function. Unlike the treatment for
`nonvesicant infiltrations, therapeutic interventions recom-
`mended for antiueoplastic vesicant extravasations vary,
`depending on the particular agent {Oncology Nursing
`Society [0N3], 1992).
`Local skin reactions caused by vesicant extravasation
`reportedly account for less than 6% of all untoward ef«
`fects of cancer chemotherapy, yet they may be a signifi-
`cant cause af discomfort, loss of function, and delay in
`the patient’s overall recovery procass. Because scientific
`advances have improved cure rates and lengthened sur-
`vival for many patients with cancer, attention to quality-
`of-life issues has become integral in the care of these pa-
`tients. Complications of cancer treatment that produce
`morbidity and disability are becoming increasingly unac-
`ceptable as tumor response and long-tenn survival become
`more commonplace. The sequelac of vesicant cxtravasation
`can seriously threaten the quality of an individual’s life.
`Therefore, strategies to reduce the incidence of extrava—
`satian and to minimize its associated morbidity are cru-
`cial. In fact, awareness of nursing management strategies
`related to extravasation is considered essantial for com-
`
`57
`
`:loyers by
`
`rig.
`
`ge Testing
`
`lfication."
`me of the
`sivestudy
`testing the
`
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`.g practice
`l'llStl'afiol'l,
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`Francisso,
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`aster, PA;
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`deadline
`
`Purpose/Objectives: To provide a comprehensive re-
`view of the literature pertinent to the phenomenon of
`onfineoplastic veslcant extravasalion within the frame—
`work of common misconceptions held by oncology
`nurses.
`
`Data Sources: Nafional guidelines, published articles
`in professional specialty journals and proceedings. and
`the authors' clinical experiences in the care of patients
`receiving vesicant agents.
`Data Synthesis: Antineopiasfic veslcant extravasatton
`can result in significant morbidity, severely limiting qual-
`ity of life for patients with cancer. It also is a liability con-
`cern for oncology nurses. Many unanswered questions
`regarding extravasation exist because the phenom—
`enon is difficult to study in humans and actual extrava—
`sotion injuries are both sporadic and underreportecl. The
`incidence of extravosation from vascular access de-
`vices is_unknown. Similarly. many recommended man-
`agement strategies are empirically based. Misconcep-
`tions about the nature at extravasation injuries and the
`manner in which they should be managed contribute to
`poor patient outcomes and increased liability.
`Conclusions: lhe disprove! of 10 myths regarding the
`nature and management of vesicant extrovosation is an
`adjunctlve step In the translation of existing national
`guidelines to workable institutional standards and ap-
`propriate professional practice.
`Nursing implications: Oncology nurses are in a strate—
`' gic pasition to observe the feasibility and efficacy of
`prevention and management guidelines established at
`national and local levels. Oncology nurses involved In
`the administration of antlneoplastic vesicant agents are ‘
`responsible for maintaining a current knowledge base
`about vesicants and for planning nursing care within the
`established standards at practice.
`
`T he parenteral infusion of any drug or solution is
`
`associated with a risk of varying degrees of tissue
`damage when infiltratiou into soft tissue occurs.
`The severity of subsequent tissue injury depends on the
`drug as well as its dose, concentration, physiochemical
`characteristics (cg, pH, osmolarily, molecular weight),
`and other irritant preperties (e.g., degrees of dissociabil-
`ity) of the infusate{Hastings-Tolsn1a, Yucha, Tompkins,
`Robson, dc Szeverenyi, 1993; Heckler, 1939; MCCaffrey
`S: Engellcing, 1990}. Additionally, the acidic vehicle in
`which an agent is reconstituted (e.g., CremapharTM Sol-
`vent Systcrn [BASE Research Triangle Park, NC]) may
`cause tissue damage (Dan, 1990). The site of extravaga-
`tion and the duration of soft tissue exposure to the agent
`also play a role (Loth & Eversrnann, 1986).
`Unless complicated by cellulitis or infection, most
`nonvesicant infiltrations result in nothing more than tran-
`
`BOYLE — VOL 22, NO 1, 1995
`
`Page 00003
`
`

`

`approaches, and panic reactions among nurses relative to
`liability. The absence of a standard nomenclature further
`contributes to the problem of quantifying and reporting
`the incidence of chemotherapy extravasation. Although a
`variety of terms are used to describe the clinical problem
`of chemotherapy extravasation, 0N3 (1992} distinguishes
`among key terms using die following definitions.
`- An t'ri'r‘rmrr is an agent that can cause aching, tightness,
`and phlebitis at the injection site _or along the vein with
`or without an inflammatory reaction.
`A vesicmtr is an agent that can cause tissue destruction.
`Vesicnnr exrr‘nvosnn‘mr is the leakage of a drugr that
`causes pain, necrosis, or sloughing of tissue into the
`subcutaneous tissue.
`Delayed extrevasarimi refers to an extravasation in
`which symptoms Occur 48 hours after the drug is ad-
`ministered.
`
`A flare is a local allergic reaction without pain that is
`usually accompanied by red blotches along the vein.
`Symptoms subside within 30 minutes with or withoat
`treatment.
`
`The standardization of infusion techniques and man-
`agement recommendations within the framework of the
`existing national standards of care (0N3, 1992) is man-
`datory both to prevent or minimize the incidence of ex-
`travasation and to improve the quality of patient out-
`comes when extravasation occurs. In addition, consistent
`and thorough documentation is critical to effectively
`communicate the nature of the problem to other health
`team members and to minimizing litigation potential. The
`goal of this article is to summarize what is currently
`known about antineoplastic vesicant extravasation within
`the framework of 10 myths associated with the nature and
`management of chemotherapy extravasation and the re-
`alities that should guide nursing practice.
`
`Myth I
`
`The incidence of extravasation injuries is well—docu-
`mented and limited to antineoplastic drug infiltra-
`tions.
`
`Although the actual overall incidence of vesicant
`extravasation is unknown, extravasation of cancer che-
`motherapeutic drugs from peripheral veins reportedly ac-
`counts for U.5%—6% of all adverse effects associated with
`
`
`
`
`
`
`
`Selected nonchemotherapeutie drugs and solutions can
`also cause local tissue necrosis if infiltrated (see Figure
`1). To date, incidence rates for extravasation of non-
`chemotherapeutic agents have not been established. The
`administration of solutions considered to be nontoxic can
`
`result in serious injury as a result of their pH, osmolarlty,
`or electrolyte composition, especially those with high
`concentrations of potassium chloride and calcium salts
`(Heckler, 1989; Seyfer & Solitnando, 1983). The admin‘
`istration of such drugs or solutions should cue the nurse
`to anticipate the risk for extravasation injury because
`many of the drugs listed may be administered concur-
`rently with chemotherapy (Viale & Yamamoto, 1993).
`
`Myth 2
`
`Extravasation of any antineoplastic agent will cause
`severe tissue necrosis.
`
`Knowledge of the Vesicant potential of chemothera—
`peutic agents is essential to the anticipation of risk for ex-
`travasation injury. A common misconception is that all
`antineoplastic agents have vesicant potential. However,
`only a small number of these agents actually are respon—
`sible for severe tissue necrosis following infiltration. Fig-
`ure 2 classifies antineoplastic drugs according to their
`vesieant or irritant potential. Vesicants frequently are
`used in a variety of multidrug regimens in the clinical set-
`ting. For a few drugs, there are only isolated case reports
`of injury following extravasation. Several antineoplastics
`are classified as irritants. While they can cause discom—
`fort, generally they do not result in the tissue necrosis and
`destruction of vital structures that is associated with vesi-
`
`cant agents. More than half of the available antineoplastic
`drugs have neither vesicant nor irritant potential.
`Initially, differentiating among actual vesicant extra-
`vasation, flare reactions (see Figure 3), and Vessel irrita-
`tion can be difficult. Sound clinical judgment is neccs-
`sary to critically evaluate these possibilities. The nature
`of the patient‘s somatic complaints, the timing of the
`onset of symptoms, the type and extent of erythema
`noted, and the location and presence of swelling are
`
`
`
`antineoplastic drug therapy (Harwood & Bachur, 1987;
`Ignoffo 8:. Friedman, 1930; Loth & Eversmann, 1986;
`Montrose, 1987). Data regarding vesicant extravasation
`from central lines is limited (Brothers et al., 1988; Lok-
`ich, Bothe, Benotti, & Moore, 1985; Wickham, 1990). A
`rare review of 329 episodes of vesicant administration
`through subcutaneous infusion ports reVealed an extrava-
`sation incidence of 6.4% (Brothers et al.). Actual occur-
`rence rates may be considerably higher than reported but
`are obscured by lack of documentation. It is possible that
`the incidence of extravasation injuries has decreased sig—
`nificantly with the use of central venous access; however,
`the use of central venous access cannot be equated with
`elimination of this clinical problem. Heckler (1989) re-
`ported that the number of patients being referred for plas-
`tic surgery to repair vesicanteinduced skin and soft tissue
`injuries is rising.
`
`Antibiotics
`Cepholothln
`Chloromphenicol
`Gentomycln
`Nofclllln
`Oxocillin
`Voncomycln
`
`Vosopressors
`Dobutomine
`Dopamine
`Epinephrine
`Motorominol
`Norepinephrine
`
`Electrolytes
`Calcium chloride
`Calcium gluconote
`Potassium chloride
`
`Other Drugs
`Dextrose > 10%
`Diozepom
`Phenytoin
`Rodiogrophic contrast
`media
`Sodium bicarbonate 8.5%
`Toto! parenteral nutrition
`solutions
`
`Figure l. Nonchemotheropeutic Drugs With Potential
`for Severe Local Reactions When lnfiltroted
`Note. Based on intern-notion from Good Samaritan Regional
`Medical Center. 1989; Heckler. 1989: Loth & Jones. 1983: Viola
`& Yomomoto, 1993: Zack. 1931.
`
`ONF- VOL 22, N01,1995
`58
`
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`

`
`
`distinguishing characteristics that should be considered
`when making a definitive assessment of local skin reac~
`tions (see Table 1).
`
`Myth 3
`
`Ulceration is immediately obvious after vesicant extra-
`vasation.
`
`Tissue destruction caused by leakage of vesicants into
`soft tissue is indolent and progressive in nature (Rudolph
`& Larson, 1987). Induration or obvious ulcer formation
`is not an immediate manifestation. Consequently, visual
`inspection of the affected area at the time of extravasation
`is not sufficient to determine the potential for or extent of
`tissue impairment.
`
`rv
`
`Evolution of Ulceration
`
`Few data describing the precise process of extrava—
`sation are available. Ulceration‘i‘s thought to develop in—
`sidiously and often is much deeper than what is initially
`evident (Laughlin, Landeen, & Habal, 1979). The effects
`of untreated vesicant extravasation are gradual, evolving
`over a series of days or longer (Loth & Eversmann, 1986).
`For example, cellular destruction associated with doxoru—
`bicin is thought to occur in a multistep process over ape—
`riod of weeks (see Table 2) (Averbuch, Gaudiano, Koch,
`& Bachur, 1986; Buchanan, Buchsbaum, O’Banion, &
`Gojer, 1985; Harwood & Bachur, 1987; Ignoffo & Fried-
`man, 1980). Maximal ulcer formation (see Figure 4) in
`terms of size and depth usually is evident two to three
`weeks postextravasation (Lebredo, Barrie, & Woltering,
`1992; Loth & Eversmann).
`The chronology of ulceration varies following extrava—
`sation of different vesicant agents. In the case of mitomy~
`cin C, a “recall” extravasation injury has been described
`in which ulceration occurs as late as 29 weeks following
`
`Common lrritants
`Carmustine
`Cisplatin
`Dacarbazine
`Etoposide
`Fluorouracil
`Mitoxantrone
`Plicamycin
`
`.
`Rare lrntants
`B'eomyc'”
`Paclitaxel
`Streptozotocln
`Tenlposide
`
`Common Vesicants
`Amsacrine
`Daciinomycin
`Daunorubicin
`Doxorubicin
`Epirubicin
`Esorubicin
`ldarubicin
`Mechlorethamine
`Menogaril
`Mitomycin C
`Vinblastine
`Vincrisfine
`Vindesine
`Vinorelbine
`Rare Vesicants“
`Cisplatin
`Mitoxantrone
`Paclitaxel
`
`Figure 2. Cancer Chemotherapeutic Agents:
`Vesicant and irritant Drugs
`0 Isolated case reports only
`Note. Based on Information from Ajani et al.. 1994; Dan, 1990;
`ONS, 1992: Peters et al., 1987.
`
`
`
`rm
`yr
`ll:
`nil
`
`
`
`Figure 3. Venous Flare Reaction
`
`initial administration (Alzawa & Tagami, 1987). In con—
`trast, Khanna, Khanna, Asthan, and Misra (1985) de—
`scribed ulceration at sites of previous blood withdrawal
`within one to three hours of mitomycin administration.
`Delayed extravasation injuries occuring Weeks following
`chemotherapy administration also have been observed
`with vindesine (Dorr, 1990). Larson (personal communi-
`cation, October 1993) points out that in his considerable
`experience evaluating and managing a variety of extrava-
`sation incidents, regardless of the agent, the ulcerative
`process can stop at any point in time, depending on local
`conditions.
`
`Clinical Manifestations
`Most extravasation research has focused on the evolu—
`tion of doxorubicin extravasations. Therefore, when de-
`scribing manifestations of extravasation injuries, doxoru-
`bicin has served as a template for studying and clinically
`monitoring all locally toxic drug infiltrations.
`The first signs of extravasation often are subtle and
`may be noted initially either by the patient or the nurse.
`The patient may report that the infusion “feels different
`than last time” or may complain of fleeting or sustained
`local burning. For example, the burning sensation expe—
`rienced with doxorubicin extravasation may be severe
`and may last from minutes to hours but eventually sub—
`sides (Rudolph, Stein, & Pattillo, 1976). At first, the nurse
`administering the agent may observe only a mild or
`blotchy redness, subtle swelling, or a change in infusion
`quality (e,g., resistance or absence of blood return on
`aspiration). Alterations in skin color in individuals with
`black or dark~toned skin may be particularly difficult to
`assess. Within days, brawny discoloration, induration, dry
`desquamation, and blistering (see Figure 5) may appear;
`these symptoms frequently are accompanied by varying
`levels of discomfort or pain. During the next several
`weeks, an ulcerative necrotic lesion requiring surgical
`excision may develop (see Figure 6). The lesions gener*
`ally begin as concentric erythematous areas; ulceration
`eventually develops centrally, and tissue damage expands
`laterally (see Figure 7) (Duray, Cuono, & Madri, 1986).
`Full—thickness skin necrosis that involves-underlying ten-
`dons and neurovascular structures and leads to permanent
`damage is not uncommon (see Figure 8).
`
`lGl
`
`rle
`
`‘,
`
`
`
`BOYLE — VOL 22, NO 1, 1995
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`
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`
`Table l. Distinguishing Characteristics of Flare Reactions, Vessel Irritation, and Extravasation
`
`Vessel Irritation Extravasation
`Characteristic
`Flare Reaction“
`Pain and burning are com—
`Aching and tightness
`mon at injection site: sting—
`ing may occur during infu-
`sion or postinfusion.
`
`itching predominates as
`major complaint: pain and
`burning are uncommon.
`
`Presenting symptoms
`
`Coloration
`
`Streaking, blotching, or
`“hive—like" erythema along
`vessel: diffuse or irregular
`pattern
`
`Erythema or dark discolora’
`tion along vessel
`
`S\~elling
`
`Unlikely
`
`Unlikely
`
`Erythema around area of
`needle; may occur proxi-
`mally at previous veni—
`puncture site placement
`
`Occurs often
`
`Usually absent or sluggish
`Usually. but not always pre—
`Usually, but not always pre—
`Blood return
`
`sent sent
`
`° Flare reactions have been described exclusively in relation to anthrocycline administration; early reports suggest that flare
`reatfiions usually do not occur with initial anthrocycline administration: additionally, symptoms of flare usually dissipate within
`30-90 minutes after initiating the infusion.
`Note. Based on information from Curran et al., 1990; Gulio, 1980; ONS. 1992; Wood Br Gullo. 1993,
`
`Extravasation Complications
`
`Chemical tissue necrosis resulting from doxorubicin
`extravasation may be complicated by ischemia, endothe-
`lial damage, and thrombosed vessels (see Figure 9). These
`subclinical effects can occur within 72 hours of vesicant ex-
`travasation (Dorr, Alberts, & Chen, 1980). Lesions of this
`severity may result in loss of circulatory integrity (arterial,
`venous, capillary), which is necessary for tissue healing, and
`in impaired physical functioning of the involved extremity.
`Linder, Upton, and Osteen (1983) described a variety of
`complications from doxorubicin extravasation that led to
`long-term morbidity in a series of 40 patients. These com-
`plications included nerve compression syndromes, perma-
`nent joint stiffness in the affected extremities, and nerve
`
`Table 2. Projected Time Line for the Evolution of
`Doxorubicin Extravasation
`Time
`
`Sequelae
`0—48 hours
`
`48—96 hours
`
`5—7 days
`
`7—21 days
`
`Initiation of cell death by DNA intercalca-
`tion; some swelling and redness is evident;
`papule formation is obvious: patient
`complains of somatic pain/discomfort.
`Dry desquamation develops; ulceration
`process begins (characterized by initia—
`tion of ischemic dermal necrosis).
`Drug disassociates from affected cells and
`binds to adjacent living cells: slow, progres-
`sive tissue damage becomes increasingly
`evident as acute edema subsides: epi—
`dem'iis becomes necrotic and ulcerated.
`
`Ulcerotion is complete: wound is charac—
`terized by well-demarcated tissue necro~
`sis; chronic multifocal inflammation is evl~
`dent atthe periphery of the necrotic area;
`surgical debridement and wide excision
`are required for pain relief and functional
`enhancement.
`
`deficits and residual sympathele dystrophies. In addition,
`myelosuppression resulting from combination therapy may
`predispose these patients to infection at the extravasation
`site (Linder et al.; Seyfer, 1987).
`
`Myth 4
`
`Clear measures to counteract tissue damage exist for
`all vesicant agents.
`
`A variety of surgical and pharmacologic interventions
`used in treating vesicant extravasation from peripheral
`veins have been reported anecdotally. Specifically, these
`measures include thermal manipulation to alter tempera—
`ture in the superficial skin, manipulating the pH of ex-
`posed tissue, and injecting antidotes into the affected
`area to reverse the action of the infiltrated agent or to
`otherwise interfere with the process of cell destruction.
`However, scientifically proven countermeasures for the
`management of vesicant extravasations are limited in
`number and are confined primarily to the treatment of
`only 8 of the 14 common antineoplastic vesicants. A
`number of interventions for vesicant extravasation have
`
`
`
`Note. Based on information from Averbuch et al., 1986; Duray
`et at, 1986; Rudolph & Larson, 4987.
`
`Figure 4. Maximal Ulcer Formation in the Dorsum of
`the Hand
`
`ONF — VOL 22, NO 1, 1995
`60
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`

`
`
`
`
`Figure 5. induraiion, Desquamation, and Brawny
`Discoloration
`
`Figure 7. Lateral Extension of Necrosis into Adiacent
`Tissue
`
`35
`.1!
`it
`is
`lit
`
`been detailed in Cancer Chemotherapy Guidelines Mod-
`ule V: Recommendations for the Management of Extra-
`vasation, Hypersensitivity and Anaphylaxis (ONS,
`1992).
`According to Larson (personal communication, Octo-
`ber 1993), cold topical applications should be used for
`immediate clinical intervention in all cases except those
`involving vinca alkaloid extravasation. Ice applications
`are readily available, simple, and nontoxic. The use of
`cold topical applications for managing cytotoxic extrava-
`sation may be effective because of their vasodilatory ef—
`fect when skin temperatures approach near~freezing. This
`resultant vasodilatory effect may influence the dilution of
`the infiltrating agent rather than alter cell metabolism or
`uptake of the infiltrate at the cellular level (Hastings—
`Tolsma et a1., 1993). Heat applications also have been
`recommended for treating extravasation. Although it is
`not clear how interstitial absorption of the vesicant is
`enhanced by heat, it is known that local warmth hastens
`the resolution of the acute phase of swelling and pain
`associated with plant alkaloid extravasations (Heckler,
`1989).
`Local antidotes currently used for treating extravasa—
`tion include dimethylsulfoxide (DMSO) applied topically
`and intradermal administration of hyaluronidase, sodium
`thiosulfate, or sodium bicarbonate. The efficacy of ste-
`roids, sodium bicarbonate, and DMSO as antidotes for
`
`
`
`Figure 6. Ulcerative Necroiic Lesion Requiring
`Surgical Intervention
`
`selected vesicants remains controversial (Jameson &
`O’Donnell, 1983; Loth & Eversmann, 1986). In fact, cor»
`ticosteroids and sodium bicarbonate have no known sci»
`
`entifically proven role in managing vesicant chemo~
`therapy extravasations, and virtually all antidotes of this
`type are “off label” at this time (Dorr, personal conununi»
`cation, September 1993).
`Despite the controversy, the use of DMSO topically
`and in solution for treating doxorubicin extravasations as
`well as continued topical application (7-14 days) of
`DMSO for treating mitomycin extravasation continues to
`be investigated (Albens & Dorr, 1991; Dorr, Sable, Lid-
`dil, & Keller, 1986; Lebredo et al., 1992; Olver et al.,
`1988). After reviewing clinical antidotes and laboratory
`investigations of antidotes for antineoplastic vesicant ex~
`travasation, Dorr (1990) concluded that further controlled
`scientific study is necessary to define appropriate and ef—
`ficacious interventions.
`
`nnyih 5
`
`The incidence and severity of extravasation injury are
`associated solely with the agent’s vesicant potential.
`
`The vesicant potential of the infusate is a primary risk
`factor for extravasation. Figure 10 lists other risk factors
`that must be considered when the administration of po—
`tentially necrotizing drugs is planned. These risk factors
`include the character of drug uptake by soft tissues, ana—
`tomic considerations for venipuncture site selection,
`needle insertion techniques, choice of intravenous de-
`vice (Wood & Gullo, 1993), as well as general risk fac-
`tors.
`
`Drug Uptake
`Key risk factors include the amount of drug actually
`extravasated and its uptake by tissues outside the lumen
`of the vein (Larson, 1982). Rudolph and Larson (1987)
`characterize antineoplastic drugs according to their up—
`take by neighboring cells, which influence ulcer severity
`and progression. Some drugs (e.g., vincristine, vinblas~
`tine) appear to cause rapid tissue damage that exhibits
`clinical characteristics similar to those found in a burn but
`are distinguished by accelerated metabolism and inactim
`vation. Hence, although the damage is immediate, the af~
`fected area heals normally with time. Other drugs (e.g.,
`doxorubicin) also produce immediate damage but are
`
`BOYLE — VOL 22, N01, 1995
`61
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`iin
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`3y
`)n
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`
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`
`Figure 8. Pre-, lntra-, and Postoperative Illustrations of
`Extravasation Injuries
`(0) Doxorubicin extravasafion on the fiexor surface of the left
`forearm; (b) Undersurface of excised skin (darkened area
`represents necrotic process retalned in tissue): (c) Operative
`result of wide excision and skin grafting (neurovascular com-
`promise is evident in hand flexion)
`
`characterized by a prolonged binding effect, which results
`in a necrotic process that occurs during a protracted con~
`tinuum of cellular destruction. The release of doxorubi—
`
`cin from dying cells and uptake b