199Immunoglobulin (Ig) therapy is the infusion of concentrated antibodies (i.e, immunoglobulins) into the vascular system. Immunoglobulins may be administered via the intravenous route (IVIg) or subcutaneously (SCIg). They are used in the treatment of both adult and pediatric patients who have an immune system deficiency or impairment and may also be used in the treatment of certain neurological and autoimmune diseases. Primary immunodeficiencies are inherited disorders of immune function that predispose affected persons to an increased rate and severity of infection, immune dysregulation with autoimmune disease and aberrant inflammatory responses, and malignancy. Because the principal clinical manifestation of immune deficiency is increased susceptibility to infection, an overarching goal of Ig replacement therapy is to decrease infections associated with antibody deficiencies. Quality of life is affected and illnesses cause missed days at work, school, and other daily activities of living. The mechanism of action of Ig in treatment of diseases is not well understood but Ig may help to bring a dysregulated immune system back into balance (Immunoglobulin National Society [IgNS], 2015).
Ig preparations are derived from large donor pools of human plasma, as many as 60,000 donors in a batch or lot (IgNS, 2015). Large pools of donors ensure a diversity allowing for recognition of many different antigens. Safety of the Ig product is ensured through careful donor screening for potential risks, inactivation methods to kill pathogens, and clearance methods to remove any pathogens from the product. Although Ig infusions have been relatively free of infectious disease transmission, a reevaluation of preparation processes was required when there was an episode of hepatitis C transmission in the 1990s (IgNS, 2015).
As with all highly specialized infusion therapies, home care nurses who administer Ig products should be experienced and should complete specific agency education and competencies. Furthermore, nurses should be familiar with the IgNS Standards of Practice (2015) that provide detailed guidance for developing organizational policies, procedures, and protocols.
After reading this chapter, the reader will be able to:
■ 200Summarize patient selection criteria
■ Differentiate between the benefits/advantages/differences between IV-versus SC-administered Ig
■ Describe key aspects of Ig administration
■ Summarize components of comprehensive care, assessment, and monitoring
■ Prepare a plan for patient education
UNDERSTANDING IMMUNOGLOBULINS: AN OVERVIEW
Immunoglobulins, along with the complement system, are the serum components of the immune system. Other major components include three types of white blood cells—T-lymphocytes, B-lymphocytes, and phagocytes. Each component has a special and essential role in resistance to infection and foreign invasion (Figure 14.1). Produced by B-lymphocytes, immunoglobulins are a family of glycoprotein molecules that are present in the body as solutes in body fluids (plasma and mucous secretions) and are attached to a group of cells in solid tissues; once attached, they inactivate and bind to antigens to facilitate phagocytosis and initiate inflammation by activating the complement cascade (Czaplewski & Vizcarra, 2014). Table 14.1 lists the five classes of immunoglobulins.
Ig products have different characteristics and these differences are believed to affect the side effect profiles of these products. No head-to-head clinical trials have been done to identify that one product over 201another is superior. Factors that vary among products include osmolarity, pH, concentration, specific antibody titers, stabilizers (e.g., amino acid based such as glycine or proline vs. sugar based such as fructose, glucose, maltose, sorbitol, or sucrose), sodium content, half-life, and form (lyophilized powder or liquid form; Sun, Teschner, & Yel, 2013). These factors are used in decision making for the most appropriate product for the patient. For example, for the patient with tendency to volume overload, a higher concentration may be used to decrease the overall volume of the infusion. However, increased concentration may also increase the risk of reactions (e.g., thrombosis). The use of products with sucrose is avoided in patients with reduced renal function because sucrose is associated with increased risk of renal failure. The amount of IgA content varies as well. This is important because patients with IgA deficiency may develop antibodies to the Ig, which is associated with increased risk for an anaphylactic reaction.
Figure 14.1 Cells of the immune system. Source: Immune System© 2013. Courtesy of the Immune Deficiency Foundation, Towson, MD.
Five Classes of Immunoglobulins
■ Largest fraction of immunoglobulin
■ Found in the bloodstream and travels to the tissues easily
■ Crosses the placenta, protecting newborn for the first few months after birth
■ Found in saliva, tears, colostrum, breast milk, intestinal and bronchial secretions
■ Prevents adherence of microorganisms to epithelial surfaces, thus helps resist infections in the respiratory, GI, and urogenital tracts
■ The first antibodies formed in response to infection
■ Largest molecules
■ Present in the circulation
■ Attacks A and B antigens in the blood leading to transfusion reactions
■ Trace amounts within blood
■ Responsible for general allergic reactions
■ Trace amounts within blood
■ Function less understood; antigen recognition
202PATIENT SELECTION CONSIDERATIONS
■ Food and Drug Administration (FDA)–approved indications based upon controlled clinical trials include:
Primary humoral immune deficiency, immune thrombocytopenic purpura, B-cell chronic lymphocytic leukemia, Kawasaki syndrome, pediatric HIV infection, multifocal motor neuropathy, chronic inflammatory demyelinating 203polyneuropathy (IgNS, 2015). Each Ig manufacturer provides specific indications for its product. A list of currently approved Ig products can be found on the Immune Deficiency Foundation at the following website: primaryimmune.org/treatment-information/immunoglobulin-products
There is evidence for additional use for Ig products with many other immune/antibody-mediated, immunomodulatory, hematological, and dermatologic disorders (e.g., autoimmune hemolytic anemia, graft vs. host disease, dermatomyositis, Guillian–Barré syndrome, myasthenia gravis, and many forms of neuropathy and myopathy; IgNS, 2015; Orange et al., 2006).
■ The patient and family are accepting of home infusion therapy.
Limitations that preclude home care include mental/physical limitations, substance abuse, psychosocial issues, presence of comorbidities, or need for closer monitoring of the disease process (IgNS, 2015). Other options for Ig infusion include outpatient clinics, physician offices, and ambulatory infusion centers.
Insurance may be a factor in choice of settings.
■ The patient is clinically stable.
The patient is tolerating the Ig without significant reactions and any transient side effects can be managed with premedication(s) (e.g., acetaminophen, diphenhydramine, and hydration, pre-, during, and postinfusion).
Review of a detailed history of the patient’s comorbid conditions and previous infusion tolerability to Ig can allow for a successful infusion.
First doses are generally not administered in the home setting (Younger et al., 2015), although some physicians/organizations may allow for a first dose of SCIg. Always refer to organizational policies and procedures.
A change in brand of Ig product or a prolonged interval (more than 8 weeks) between Ig infusions should deem the patient Ig-naïve and at greater risk for adverse events (IgNS, 2015).
■ An appropriate vascular access device is planned for Ig administration.
Most often, a short peripheral IV catheter is used to administer each IVIg infusion.
For patients with poor venous access or compromised vascular integrity, a long-term central venous access device such as an implanted venous access port may be placed if SCIg or other alternatives are not available (IgNS, 2015). Due to the risks of infection and thrombotic complications associated 204with central vascular access devices, the American Academy of Allergy, Asthma, and Immunology does not support the use of implantable ports as best practice, unless there are circumstances that require multiple therapies being used to treat the patient (Orange et al., 2006).
■ IVIg versus SCIg: Factors that favor SCIg include difficult vascular access, systemic adverse effects with IVIg, or suboptimal health at trough period when IVIg is due, and increased risk for thrombotic events or hemolysis (Bonilla & Duff, 2015).
■ The home environment is safe, clean, with adequate refrigeration, adequate light, electricity, and the patient has ready access to a telephone. There is reasonable access to emergency services should a severe reaction occur.
■ Reimbursement is verified.
Private third-party payers vary in coverage and whether there is access to an additional carve out for specialty pharmacy benefits.
The Medicare IVIG Access Act (HR 1845) was signed into law on January 10, 2013, as a 3-year demonstration project to examine the cost-effectiveness of home IVIg infusion administration (Centers for Medicare and Medicaid Services [CMS], 2016; “Medicare Intravenous Immune,” n.d.). This Medicare law contains a special provision for patients with primary immunodeficiency diseases (PIDD) to receive home infusions of IVIg under Medicare Part B. Medicare will provide a bundled payment under Part B for items and services that are necessary to administer IVIg in the home to enrolled beneficiaries who are not otherwise homebound and are receiving home health care benefits. The demonstration applies only to situations where the beneficiary requires IVIg for the treatment of PIDD, or is currently receiving subcutaneous immune globulin to treat PIDD and wishes to switch to intravenous immune globulin. Services are covered through this law through September 30, 2017.
COMPREHENSIVE CARE, ASSESSMENT, AND MONITORING
Plan for Home Care and Visit Frequency
■ Unlike most other home infusion therapies and in contrast to SCIg, self-care with IVIg infusions is not the usual goal. Because 205there is a risk of adverse reactions with each infusion, in most cases the home care nurse administers the IVIg, monitors, and remains in the home for the entire infusion. In one study, treatment outcomes including adherence to therapy and decreased cost of care were improved with nurse-administered home infusion (Luthra, Quimbo, Iyer, & Luo, 2014).
■ Schedule home visits to coincide with the time of IVIg administration.
■ A typical IVIg home infusion may run over several (e.g., 3–4) hours.
■ IVIg infusions are generally administered every 2 to 4 weeks, based on the patient’s diagnosis, IgG levels, and response to therapy.
■ A follow-up telephone call is recommended 2 to 3 days after infusion to assess for any side effects post-Ig infusion.
■ Ensure that orders include name(s) of Ig product/concentration, dosage (some products recommend a dose adjustment factor), route, frequency of infusion, rate and method of administration.
Verify presence of, and orders for use of, a nonexpired anaphylaxis kit (e.g., contents of epinephrine and diphenhydramine) or epinephrine prior to attempting peripheral catheter placement for IVIg or initiating SCIg due to an ongoing risk of reaction (IgNS, 2015).
Compare and verify orders of Ig product to physician’s order.
■ SCIg administration: Advantages of SCIg include a more steady state of IgG levels due to frequency of dosing, less systemic side effects than IVIg, and the ability for total self-care as patients learn how to self-administer infusions.
Home care nurses are usually responsible for assisting in the initial training for self-infusion of SCIg infusions (will require several visits based on the patient and the type of product).
SCIg infusions are administered at regular intervals from daily up to every 2 weeks (biweekly). Individualize the dose based on the patient’s clinical response.
The maximum fluid volume of conventional SCIg (10%–20% concentration) per site is usually limited to 15 to 60 mL based on specific product recommendations; this may require infusion into more than one site; up to eight sites may be simultaneously used (IgNS, 2015).
206There is an SC product that uses recombinant human hyaluronidase to facilitate the dispersion and absorption of Ig. The enzyme is administered first then followed by the Ig product within 10 minutes, administered in the upper abdomen or thighs. Always refer to the manufacturer’s prescribing information (HyQvia Prescribing Information, 2016).
In conventional SCIg, the abdomen is preferred by many patients due to adequacy of subcutaneous tissue, but other options include thighs, back of upper arms, and lower back.
Although there is limited evidence, the practice of aspirating the SC device for absence of a blood return prior to SC infusion is recommended by IgNS (2015) and Infusion Nurses Society (INS; Gorski et al., 2016). There is ongoing discussion of this practice and it has been suggested as a topic for further research.
Usual administration is via a mechanical or electrical mechanical syringe driver infusion pump but patients may also choose to manually push the SCIg (Shapiro, 2013).
Local site reactions including swelling, itching, mild to moderate pain, localized warmth, and erythema are common and tend to resolve with 24 to 48 hours after infusion. Note that local reactions tend to diminish over time.
SC needle length can be a critical factor that may influence tolerability. Children and very thin patients may need a 6-mm needle. Most average-sized patients will use a 9-mm needle. Longer needle lengths (12, 14 mm) may be required for some patients (Younger et al., 2015).
■ IVIg administration: Administration methods for IVIg vary based on issues such as infusion rate, concentration (3%–12%), formulations (stabilizers), osmolality, and safety concerns.
Ambulatory or stationary electronic infusion devices are preferred for more consistent rate control.
Gravity drip may also be used in conjunction with a rate control device such as a manual flow regulator administration set.
Many IVIg preparations are in the liquid form, ready for use for room temperature delivery. A few require reconstitution and, following manufacturer’s instructions, usually include the use of transfer device.
The home care nurse reconstitutes the product just prior to administration (after vascular access is established).
Whether reconstituted or liquid form, product may be transferred to a larger IV bag for administration.
207If liquid form is used directly from glass container, vented pump tubing is required.
Key points related to reconstituting include: use strict aseptic technique; allow adequate time for product to dissolve (varies, less than 5 minutes up to 20 minutes); gently swirl vials to dissolve but never shake.
Some products may recommend use of a filter (most do not).
Record product lot number and expiration date; this is recommended in the event of a product recall or need to follow up on a product lot.
■ Verify patient identification and verify infusion rate on pump.
Follow orders/manufacturer’s guidelines for rate.
Initiate infusion slowly, increasing rate as infusion is tolerated.
Too rapid infusion may cause headache and hypotension; symptoms usually resolve with slowing infusion rate.
■ Reinforce patient education of when and to whom related signs/symptoms/infusion issues should be reported to the health care professional team (e.g., side effects to physician/pharmacist/nurse vs. infusion pump/ancillary issues to speciality pharmacy).
■ General guidelines to prevent and manage adverse reactions (IgNS, 2015):
Decrease infusion rate and divide large doses and administer on different days.
Consider a product substitution.
Change from IVIg to SCIg, if appropriate.
In some cases, premedications may be required (e.g., analgesic, antipyretic, and antihistamine prior to IVIg infusion). Steroids may be required for patients with a history of side effects and/or limited product tolerance.
Monitor urine output and provide adequate hydration (oral or IV) to reduce risk of inflammatory reactions, thromboembolic events, and renal complications.
Assessment and Monitoring
The patient receiving IVIg therapy is monitored during the infusion for any adverse reactions. Systemic reactions are more common with IVIg and local site reactions more common with SCIg (IgNS, 2015). The most common adverse reactions include headache, nausea, blood pressure changes, flushing, myalgia, arthralgias, urticarial, low-grade fever, chills, chest discomfort, and tachycardia. Significant adverse events include aseptic meningitis, acute renal failure, thrombotic 208complications, hyperproteinemia, risk of transmitted infection, transfusion-related lung injury (TRALI), hemolytic anemia, and anaphylaxis (IgNS, 2015).
With each infusion, assess/monitor as follows:
■ Identify any significant changes in health status prior to each infusion (e.g., respiratory rate, breath sounds, changes in weight, presence of any acute illness, and infection); changes in weight may require a modification of the Ig dose.
■ Review laboratory data as appropriate collected prior to the start of the IVIg infusion:
Serum IgG trough levels, complete blood count (CBC), serum creatinine, blood urea nitrogen (BUN), electrolytes, and hepatic profile (Czaplewski & Vizcarra, 2014)
■ Examine vital signs:
Check prior to initiating each IVIg infusion, at regular intervals according to orders/organizational policies, and at the end of the infusion. With long-term stable patients, the frequency for monitoring vital signs may be reduced based on physician discretion.
Fast Facts in a Nutshell