Supportive care of the patient receiving chemotherapy continues to gain recognition as an equally important component of definitive therapy. Advances have been possible through the study of evidence-based interventions and guideline development. Contributions to the substantial improvements include better understanding of the pathophysiology of specific side effects, increased knowledge and attention to risk factors, and availability of newer agents for prevention and management of side effects. The side effects of cancer chemotherapy can be acute or prolonged, and can be mild or severe in nature. Specific cancer patient populations may be at higher risk for complications. The growing elderly population is often affected by cancer, and may also have multiple comorbidities, complicating the tolerance of treatment. Many chemotherapy regimens are complex, especially with concurrent chemotherapy and radiation therapy, common in cancers of the head/neck, esophagus, and lung. Treatment of patients with advanced disease is particularly challenging, as many have existing symptom issues in addition to those caused by treatment, increasing the need for palliative care. Although much progress has been made, the management of side effects continues to be of utmost importance for the tolerability of therapy and effect on overall quality of life. Inadequately controlled side effects may also lead to increased use of health care resources and costs, and may occasionally impact adherence to therapy. The implementation of evidence-based interventions is critical in making appropriate clinical decisions for patient safety and the management of side effects. Reduction of symptoms and complications is also important in preventing hospital admissions, and may ultimately affect reimbursement.
II. INFUSION-RELATED COMPLICATIONS
A. Extravasation
Extravasation is an acute, infusion-related complication that should be considered an oncologic emergency. Extravasation occurs when a chemotherapy agent is inadvertently administered into the perivascular space or subcutaneous tissue, instead of into the vein. The severity of the extravasation damage depends on the specific type of drug, the length of time the tissues are exposed, and the concentration and amount of drug extravasated, the location of the extravasation, and other patient factors such as older age, comorbidities, and impaired immunocompetence.1 Extravasation injury to the tissues can range from local irritation to severe necrosis.
1. Classification
Chemotherapy drugs are often grouped into categories according to their potential to cause tissue damage due to extravasation. Vesicant drugs are those capable of causing pain, edema, erythema, and necrosis of the tissues when administered outside the vein. Vesicants are further categorized as DNA-binding and non-DNA-binding agents. The vesicant can bind to nucleic acids in the DNA of healthy cells in the tissue, causing cell death or apoptosis. There is a continued cycle of tissue damage as the agent is retained. DNA-binding vesicants include the anthracyclines (daunorubicin, doxorubicin, idarubicin, and epirubicin). In agents that are non-DNA binding, the tissue injury is mild to moderate and more localized, as the drug is eventually metabolized in the tissue and neutralized.1,2 Examples of non-DNA-binding agents include the plant alkaloids (vinblastine, vincristine, vinorelbine) and the taxanes (docetaxel, paclitaxel, and paclitaxel protein-bound particles). One of the difficulties in the vesicant designation of the taxanes is that there are some recommendations against infusing vesicants peripherally for more than 30 to 60 minutes. Paclitaxel, for example, is often infused peripherally over 1 to 3 hours. Current available literature supports the safety of the administration of the taxanes through peripheral access at the recommended concentrations and durations.3 Further updates are needed to clarify these practice guidelines.
Irritant drugs may cause redness and pain in the affected vein or extravasation site, but do not often lead to tissue necrosis. Ulceration is unlikely unless a large volume of concentrated drug has extravasated.
2. Risk factors
Risk factors for peripheral extravasation that are patient-related include small, fragile veins, multiple previous venipunctures, prior treatment with irritating or sclerosing drugs, diseases with impaired circulation, impaired cognition, and communication difficulties. Procedure-related risk factors include multiple venipuncture attempts, nonoptimal sites (antecubital fossa, back of hand, inner wrist), and inexperienced personnel. Risk factors for extravasation from central venous access devices include inadequate access or securing of the noncored needle, deeply implanted ports, and lack of patency or blood return.1
Safe administration practices, implementation of policies and procedures, and education of staff are all measures to assist in the prevention of extravasation episodes. Patients should also be educated on the signs and symptoms of extravasation, prior to their first treatment. Early identification of potential extravasation is important in preventing further exposure and prompt initiation of antidotes. Common signs and symptoms of extravasation are pain or burning at the intravenous (IV) site, redness, swelling, inability to obtain a blood return, and change in the quality of the infusion. Any of these complaints or observations should be considered a symptom of extravasation until proven otherwise. Table 26.1 lists common actions should a peripheral or central extravasation be suspected.1,2,4
TABLE 26.1 Procedures to Manage Peripheral and Central Extravasations
1.
Stop administration of the chemotherapy agent.
2.
Leave the needle/catheter in place, and immobilize the extremity.
3.
Attempt to aspirate any residual drug in the tubing, needle, or suspected extravasation site.
4.
Remove peripheral IV or port needle.
5.
Assess the suspected site of extravasation and patient symptoms.
6.
Notify the physician or midlevel provider.
7.
Administer the appropriate antidote, as shown in Table 26.2. This may include instillation of a drug antidote or application of heat or cold to the site. Consideration for antidote order sets and verification of antidote accessibility is recommended prior to administration.
8.
Provide the patient and/or caregiver with instructions, including the need to elevate the site for 48 hours and the continuation of antidote measures as appropriate.
9.
Discuss the need for further intervention with the physician, and photograph if indicated.
10.
Document extravasation occurrence according to institutional guidelines.
11.
Continued monitoring of extravasation site at 24 hours, 1 week, 2 weeks, and additionally as guideline recommends. Secondary complications such as infection and pain may occur. Follow-up photographs at these time periods, if possible, are helpful in monitoring extent of injury and progress in healing.
12.
Other imaging may be done for central extravasation (chest X-ray, CT scan, venography).
13.
Surgical consultation (vascular and/or plastic surgery) may be done for central extravasations or in any extravasation that may require further interventions.
Source: Polovich M, Olsen M, LeFebvre KB. Chemotherapy and biotherapy guidelines and recommendations for practice. 4th ed. Pittsburgh: Oncology Nursing Society; 2014 and Boulanger J, Ducharme A, Dufour A, et al. Management of the extravasation of anti-neoplastic agents. Support Care Cancer. 2015;23:1459-1471.
3. Management strategies
There is very little evidence-based data on management of extravasation and antidote use. Currently, dexrazoxane has the most data in treating anthracycline extravasation, with greater than 98% efficacy.1,2 The only US Food and Drug Administration (FDA)-approved product for the treatment of anthracycline extravasation, Totect, has not been commercially available from the manufacturer, with time of availability unknown. In the interim, generic dexrazoxane, or Zinecard, is an option for use. Much of the data on the other antidotes and surgical interventions for central extravasations such as lavage are anecdotal or based on case reports. Surgical lavage within 12 hours of a central extravasation may have some benefit; however, the outcomes may be less favorable for extravasations greater than 50 mL and the nature of the extravasated agent.5 See Table 26.2 for common chemotherapy agents and management guidelines.
4. Administration practice change: vincristine
Guidelines for the administration of vincristine via mini-bags have been recommended by several national and international organizations, such as the World Health Organization (WHO), Institute for Safe Medication Practices (ISMP), and The Joint Commission (TJC). While it is often common practice to administer vesicants via syringe as an IV sidearm push, the use of minibags is essential in the prevention of inadvertent intrathecal administration of vincristine.
Although there may have been initial resistance to the adoption of this guideline, many organizations adhere to this practice. The concern for risk of extravasation has been found to be minimal, and the mini-bag use has been found to be safe, practical, and feasible.6
B. Infusion reactions: anaphylaxis, hypersensitivity reactions (HSRs), and cytokine-release reactions
Infusion reactions are considered an oncologic emergency associated with chemotherapy administration. Specific drugs with the potential for hypersensitivity with or without an anaphylactic response should be administered under the constant supervision of a competent and experienced nurse and with a physician or midlevel provider readily available, preferably during the daytime hours. Important preassessment data to be documented include the patient’s allergy history, though this information may not predict an allergic reaction to chemotherapy. Patients who are currently prescribed beta blockers and angiotensin-converting enzyme inhibitors may have increased severity of an anaphylactic reaction and may have difficulty responding to effective anaphylactic treatments.7 Furthermore, cardiovascular and pulmonary disorders may also complicate the patient’s ability to tolerate a HSR. Other risk factors include previous exposure to the agent and failure to administer effective prophylactic medications. Chemotherapy drugs with the highest risk of HSRs are asparaginase, the taxanes (e.g., paclitaxel and docetaxel), and platinum compounds (e.g., cisplatin, carboplatin, and oxaliplatin). Carboplatin is the agent with the most reported HSRs in patients with ovarian cancer. In patients receiving more than seven cycles, the incidence of HSRs is 27%. BRCA carriers are at greatest risk, and up to 40% of BRCA+ ovarian cancer patients can be sensitized after 10 exposures.8 Drugs with a low to moderate risk include the anthracyclines, bleomycin, IV melphalan, etoposide, and humanized (e.g., trastuzumab) or chimeric (e.g., rituximab) monoclonal antibodies.
TABLE 26.2 Common Vesicant and Irritant Drugs and Potential Antidotes
Chemotherapy Agent
Pharmacologic Antidote
Nonpharmacologic Antidote
Method of Administration
▪ Mitomycin
▪ Dactinomycin
No known drug antidote
Topical cooling
Apply ice pack for 15-20 minutes at least four times a day for the first 24 hours
▪ Doxorubicin
▪ Daunorubicin
▪ Epirubicin
▪ Idarubicin
Dexrazoxane (Totect)
Topical cooling
Dexrazoxane should be used as soon as possible and within 6 hours of the anthracycline extravasation. Administration of dexrazoxane is IV for 3 consecutive days (day 1:1,000 mg/m2; day 2: 1,000 mg/m2; day 3: 500 mg/m2) into a large vein in an area other than the extravasation area (i.e., preferably the opposite arm) over 1-2 hours. Apply ice pack for 15-20 minutes at least four times a day for first 24-48 hours. Topical cooling should be removed 15 minutes before, and during, dexrazoxane administration
Apply heat for 15-20 minutes at least four times a day for first 24-48 hours Hyaluronidase is instilled as five 0.2 mL injections SC into extravasated area, using a small-gauge needle (25 g). Change needle with each injection. Hyaluronidase is stored in refrigerator
▪ Oxaliplatin
Case reports that use of high-dose dexamethasone (8 mg twice daily for up to 14 days) has reduced inflammation
Warm compresses
A warm compress applied to extravasation site is preferable
▪ Docetaxel
▪ Paclitaxel
▪ Paclitaxel protein-bound particles
None
Topical cooling
Apply ice pack for 15-20 minutes at least four times a day for first 24 hours
IV, intravenous; SC, subcutaneously.
Source: Polovich M, Olsen M, LeFebvre KB. Chemotherapy and biotherapy guidelines and recommendations for practice. 4th ed. Pittsburgh: Oncology Nursing Society; 2014 and Boulanger J, Ducharme A, Dufour A, et al. Management of the extravasation of anti-neoplastic agents. Support Care Cancer 2015;23:1459-1471.
1. Types of reactions
Type 1 HSRs (which may or may not be immune-mediated) are the most common chemotherapy-induced type of reactions. These reactions characteristically occur within 1 hour of receiving the drug; however, with paclitaxel, the HSRs often occur within the first 10 minutes of the start of the infusion. Common manifestations of a grade 1 or 2 type I reaction include flushing, urticaria, fever, chills, rigors, dyspnea, and mild hypotension. Grade 3 and 4 reactions may involve bronchospasm, hypotension requiring treatment, angioedema, or symptoms requiring hospitalization. Less common signs and symptoms of infusion reactions include back or abdominal pain, nausea, vomiting, and diarrhea, incontinence, and anxiety. With appropriate premedication, the incidence of the HSRs has markedly decreased. Commonly used premedications include dexamethasone, diphenhydramine, and an H2-histamine antagonist such as cimetidine, ranitidine, or famotidine. Emergency equipment should be immediately accessible, including oxygen. The following parenteral drugs should also be stocked in the treatment area: epinephrine 1:10,000 solution, diphenhydramine 25 to 50 mg, methylprednisolone 125 mg, and dexamethasone 20 mg.1 The development of a clinical guideline for HSRs, with or without true anaphylaxis, may be helpful in preparing for a potential reaction, reducing delays in response time to a reaction, and standardizing the management of a reaction with standing orders. Table 26.3 is an example of a HSR standing order guideline.
2. Cytokine-release reactions, which are commonly referred to as infusion reactions, are a symptom complex that occurs most frequently when monoclonal antibodies are administered. This type of reaction is believed to be primarily related to the release of cytokines from targeted cells and other immune cells. Most monoclonal antibodies have the potential to cause this syndrome, and the appearance may be similar to the type I HSR. In contrast, however, the cytokine-release reactions may be managed by short-term cessation of the infusion, administration of histamine blockers, and restarting the infusion at a slower rate, that is, 50% after resolution of symptoms. Table 26.4 compares the differences between chemotherapy and biotherapy infusion reactions.1,7,8,9
TABLE 26.3 Sample Standing Orders for Hypersensitivity Reactions to Chemotherapy Agents
Have the following medications available:
▪ Diphenhydramine 50 IV
▪ Methylprednisolone 125 mg IV or equivalent hydrocortisone
▪ Epinephrine (1:10,000 solution)
1.
If signs/symptoms of hypersensitivity occur (such as urticaria [hives], respiratory distress, bronchospasm, hypotension, angioedema, flushing, chest/back pain, anxiety), stop infusion of chemotherapy/biotherapy agent.
2.
Maintain IV access with IV normal saline at 200 mL/hour until blood pressure stabilizes.
3.
Administer oxygen at 2-4 L/minute, and measure pulse oximetry.
4.
Administer methylprednisolone 125 mg IV push.
5.
Administer diphenhydramine (Benadryl) 50 mg IV push.
6.
Continuously monitor blood pressure, pulse, and oxygen saturation.
7.
Notify physician immediately for further orders.
8.
If symptoms do not resolve or worsen, administer epinephrine as directed by physician.
9.
Initiate a code if airway patency is not maintained or cardiopulmonary arrest occurs.
IV, intravenous.
Source: Polovich M, Olsen M, LeFebvre KB. Chemotherapy and biotherapy guidelines and recommendations for practice. 4th ed. Pittsburgh: Oncology Nursing Society; 2014 and Vogel WH. Hypersensitivity reactions to antineoplastic drugs. In: Yarbro CH, Wujcik D, Gobel BH, eds. Cancer symptom management. 4th ed. Burlington: Jones & Bartlett Learning; 2014:115-130.
3. Risk stratification testing
Test doses or skin tests may be performed if there is an increased suspicion for hypersensitivity. Standardized testing has not been established, and different testing concentrations have been reported. It is recommended to wait at least 2 to 4 weeks following the initial reaction to test dose, to ensure that the skin test is not falsely negative. This is most commonly done for platinum agents. Carboplatin skin testing sensitivity has been reported at 85.7%, with an 8% to 8.5% false-negative rate. Repeated skin testing has been recommended for risk stratification, as patients with a negative skin test could convert to a positive skin test result with subsequent testing.8,10 A skin testing protocol for carboplatin skin testing is shown in Table 26.5.
TABLE 26.4 Infusion Reactions: The Comparison of Chemotherapy and Biotherapy Agents
Characteristic
Chemotherapy
Biotherapy
Reaction type
Type I hypersensitivity
Cytokine release
Timing of reaction
Platinum: after multiple cycles (Carboplatin >7 cycles)
Most monoclonal antibodies: first infusion
Taxanes: first or second infusion
Rituximab: any infusion
Prevention
Premedication
Premedication
Management/rechallenge
▪ Grade 1 or 2: premedication—reinitiate infusion at slower rate
▪ 2: Infusion interruption; responds promptly to symptomatic treatment (drugs, fluids); prophylactic medications indicated for ≤24 hours
▪ 3: Prolonged/recurrences of symptoms after initial improvement; hospitalization indicated
▪ 4: Life-threatening; pressors or ventilator needed
▪ 5: Death
Source: Polovich M, Olsen M, LeFebvre KB. Chemotherapy and biotherapy guidelines and recommendations for practice. 4th ed. Pittsburgh: Oncology Nursing Society; 2014; Vogel WH. Hypersensitivity reactions to antineoplastic drugs. In: Yarbro CH, Wujcik D, Gobel BH, eds. Cancer symptom management. 4th ed. Burlington: Jones & Bartlett Learning; 2014:115-130; Castells MC. Anaphylaxis to chemotherapy and monoclonal antibodies. Immunol Allergy Clin North Am. 2015;35:335-348; and National Cancer Institute Cancer Therapy Evaluation Program. Common terminology criteria for adverse events (CTCAE) (Version 4.03); 2010. Retrieved from http://evs.nci. nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5×11.pdf
Tryptase is a protease that is present in all human mast cells. Tryptase is released from mast cell granules during allergic and anaphylactic reactions, within 30 to 60 minutes from the onset of symptoms. An elevated tryptase level (>11 ng/mL) drawn at the time of the reaction may be helpful in determining the indication for desensitization. If the serum tryptase level is elevated, a subsequent level is needed to screen for mastocytosis.8,11
All patients receiving their sixth and subsequent doses of carboplatin will have skin test dosing.
2.
The planned carboplatin dose is diluted in 50 mL of 0.9% sodium chloride. A 0.02-mL aliquot is withdrawn and administered intradermally.
3.
Following the intradermal injection, the injection site is examined at 5, 15, and 30 minutes.
4.
A positive skin test is a wheal of ≥5 mm in diameter, with surrounding redness. A strongly positive skin test was one with ≥1 cm in diameter. If a patient develops a positive skin test, the physician is notified.
5.
If the skin test is negative, the patient is then pretreated for the carboplatin with antiemetics, dexamethasone, diphenhydramine, and famotidine. Thirty minutes after the premedications are given, the carboplatin is given.
Source: Patil SU, Long AA, Ling M, et al. A protocol for risk stratification of patients with carboplatininduced hypersensitivity reactions. J Allergy Clin Immunol. 2012;129(2):443-447; Calado J, Picard M. Diagnostic tools for hypersensitivity to platinum drugs and taxanes: skin testing, specific IgE, and mast cell/basophil mediators. Curr Allergy Asthma Rep. 2014;14:451; and Blatman KS, Castells MC. Desensitizations for chemotherapy and monoclonal antibodies: indications and outcomes. Curr Allergy Rep. 2014;14:453.
Only gold members can continue reading. Log In or Register to continue
