CHAPTER 11

Allergic Emergencies

The practice of office allergy has been compared with flying: hours of calm interspersed with occasional moments of stark terror. Those engaging in this practice must be constantly mindful that they are injecting patients with an antigen that may at any time potentially precipitate a life-threatening anaphylactic reaction. Obviously, the preferred approach is the prevention of such an emergency situation, and this chapter outlines steps aimed at just such a purpose.

Because bad things sometimes happen to good people, however, despite our best efforts, the appropriate management of an allergic emergency is also discussed. In the same fashion as a flight attendant calling your attention to the emergency procedure card located in the airplane seat pocket, we suggest you read this information carefully and hope you never need to use it.

PREVENTION OF ALLERGIC EMERGENCIES

Although it is mandatory that every health care provider who deals with allergy immunotherapy be well versed in the management of allergic emergencies, it is much better to avoid the occurrence of such crises altogether. Thus, it is worthwhile to devote some attention to measures that minimize the risk for anaphylaxis associated with allergy immunotherapy. Happily, the authors can attest to the effectiveness of these safeguards in their own practice of otolaryngic allergy.

Initial Testing Methods

The first important measure is the use of quantitative testing methods as a basis for immunotherapy. With intradermal dilutional testing (IDT), skin testing is begun at an anticipated nonreactive antigen dilution, and concentrations are advanced in fivefold steps until reactivity is observed and confirmed. This methodology immediately identifies the threshold of reactivity for each antigen to which the patient is sensitive, and allows the practitioner to avoid the introduction through testing or treatment of excessive amounts of that antigen.

The final test to ensure safety is the initial in vivo test of the treatment vial. If no errors in compounding have occurred, this may be unnecessary in the case of IDT-based therapy, as testing and treatment vials have come from identical antigen sources in the stock vials. However, vial testing remains an excellent “fail-safe” measure to avoid any possible reactions resulting from errors in compounding the treatment vial. In vitro-based therapy must always include a vial test, as it is not certain that the antigens in the treatment vial are anti-genically the same as those used in the testing laboratory. Details of the vial test concept are presented in Chapter 10.

When a new stock vial of an antigen is obtained, even though it comes from the same manufacturer that provided the previous vial, it may not have the same antigenic potency as the one it is replacing. In this situation, vial tests of new treatment mixes made after such a change are a useful safety measure. As a practical matter, however, it is not always necessary to perform such vial testing if the antigen manufacturer is the same, and their quality control is good. On the other hand, if antigen is obtained from a new manufacturer, vial tests or even parallel IDT determinations using the old and new material may be necessary to avoid unnecessary reactions. Parallel IDT test comparison is always the best practice when switching from a weight/volume (w/v) antigen to a standardized antigen extract.

Some patients are recognized as “brittle,” or highly sensitive, with a high potential for reactions to skin testing or injections. The prime examples of such high-risk patients are those with asthma.¹ Others in this category include patients with urticaria, those with a history of prior severe reactions to allergy skin testing or injections, and patients suspected of having sensitivities to a great many allergens. These patients should be tested by in vitro means when possible, and if skin testing is required, they should have tests administered beginning at a very low concentration (usually #6 IDT dilution). Furthermore, it may be wise to limit the number of antigens tested for at any one sitting, to avoid a cumulative effect of numerous positive reactions in possibly producing a systemic reaction. A common error is testing for numerous antigens in the same or cross-reacting families, which effectively administers a higher dose of that antigen. This is most important when skin testing grasses. In most areas, it is sufficient to test with only Bermuda and Bahia grasses and with one Pooid grass, such as Timothy or Fescue. Placing additional wheals at higher concentrations after the confirming wheal has occurred is another way in which an unacceptable antigen load may be administered during testing. As a practical matter, if IDT is correctly performed (including proper antigen selection and not progressing past a confirming wheal), a reaction is unlikely to occur. Unless individual circumstances dictate otherwise, however, testing should probably be limited to 12 to 15 antigens per sitting. Finally, testing personnel should be trained to stop testing when they observe an unusual number of large wheals developing during a test session.

Reactions are more likely to occur during advancement immunotherapy than during skin testing, and this risk is heightened when the antigens in question are “in season.”^2,3

Dose Advancement

The first injection from any new treatment vial should ideally be administered in the physician’s office, because there is potential for an abrupt effective dose increase with a freshly made vial.³ Thereafter, dose advancement should be modified as circumstances change. One can never completely place a patient on a routine schedule for dose advancement without consideration of changes in allergic load, complicating infections, and similar modifying factors. The dose should be advanced to the maximum tolerated dose, with the realization that local (and systemic) reactions indicate the need for modification of dose schedules. If continued reactions occur despite appropriate dose adjustments, it is often best to discard the treatment vial in use and begin again. The effort involved in remaking a vial is small, whereas the costs of dealing with anaphylaxis are large and not simply measured in units of time and money.

Human Errors

The possibility for error in the allergy office exists at every step, from testing to vial formulation to administration of immunotherapy. Measures to avoid allergic reactions begin with adequate training of the person responsible for testing, so that proper technique and procedure are followed. It is a good idea to have the physician or another member of the allergy team double-check the determination of end points and the mathematics of vial preparation from the data obtained. It must be emphasized that the person preparing vials should do so in an environment totally free from interruptions and distractions, to minimize lapses in concentration and possible compounding errors. During mixing, labels should be preattached to mixing vials, and mixing technique should be checked and double-checked. If ever the mixing process is interrupted, or the person preparing a vial becomes uncertain of a vial’s contents, that vial should be discarded, and a new one made.

If properly performed, IDT is a safe means of skin testing for inhalant allergy. However, if additional wheals are placed beyond the “confirming wheal,” overdosing is possible. Correct interpretation of the test results is also necessary to assess accurately the antigen concentration that will be included in the initial treatment vial. After end points have been determined (either from IDT or in vitro), accurate calculations and mixing are necessary to prepare the treatment vial, and errors in this process can have disastrous results. One of the most common (and potentially catastrophic) errors is a misplaced decimal point, either in calculations of dose or in drawing up the appropriate volume for injection. This is particularly a problem if injections are given in an office that is relatively unfamiliar with allergy treatment, and is used to giving 0.5 or 1.0 mL shots. Reactions have ensued after a dose of 0.05 mL has been confused with one of 0.5 mL, providing a 10-fold overdose of antigen.

The administration of injections from the treatment vial requires that the vial of the correct patient be chosen from all the available vials (Fig. 11-1) and that the proper dose be given. The opportunities for disastrous consequences of a mistake are obvious. When an injection is administered, the patient’s identity should be checked against the vial label, and the dose administered should be carefully scrutinized. To avoid any such misidentification, the authors advise that the treatment vial be shown to the patient, who is asked to confirm its identity (Fig. 11-2). Birth dates should also be used whenever two patients with similar or identical names are on treatment. Color-coded vials may be used when more than one patient in a family is on home treatment.

In short, allergy testing and treatment present numerous opportunities for errors that can possibly result in anaphylaxis. The prevention of these errors requires constant and meticulous attention on the part of the allergy nurse or assistant.

True allergic reactions may be immediate or delayed. These should be differentiated from nonallergic, vasovagal reactions, which are (fortunately) much more common than true allergic reactions. Both immediate and delayed reactions may be local or systemic. Local reactions are characterized by induration (wheal) surrounded by erythema (flare) (Fig. 11-3). The size of the wheal (not the flare) is the determining factor in altering subsequent immunotherapy doses.

Delayed allergic reactions may be either local or systemic, and the former are much more common than the latter. A significant delayed local reaction is characterized by an area of induration and redness greater than 30 mm in diameter (i.e., larger than a half-dollar coin) at the site of a previous injection. Delayed systemic reactions are generally manifested as an increase in the patient s usual allergic symptoms, but symptoms may also include urticaria, arthralgias, or constitutional symptoms involving almost any organ system.

Delayed allergic reactions are generally of the Gell and Coombs type III. They are most often seen in association with allergy to molds. These reactions typically occur from 6 to 36 hours after an injection (or skin test), and thus do not occur while the patient is in the office or has just had the injection or test. It is therefore important not only to educate patients about the possible occurrence of such reactions, but also to advise them regarding proper treatment measures. The treatment of a delayed local reaction generally requires only the administration of one or more doses of an antihistamine, sometimes augmented by application of ice to the reaction site followed by a topical steroid cream or ointment. However, it is important that these reactions be reported so that appropriate adjustment of the immunotherapy dose can be made if they occur regularly.

The treatment of vasovagal reactions is recumbency, reassurance, and time. This is generally augmented by placing a cold cloth to the forehead and administering a whiff of an ammonia ampule. Although not a required therapeutic maneuver, oxygen administered by a mask is sometimes reassuring. The most important part of managing a vasovagal reaction is differentiating it from anaphylaxis.

Anaphylactic reactions are of the immediate type and represent a Gell and Coombs type I event. Their importance lies in their potential for rapid progression to an ultimately fatal outcome. Therefore, it is important to recognize their characteristic signs and symptoms (Table 11-1). In anaphylaxis, the organs richest in mast cells (respiratory tract, blood vessels, skin) are primarily affected. The onset of anaphylaxis is generally seen within 15 to 20 minutes of the allergic event and almost never begins after 45 to 60 minutes have passed.^3,4