Key words: anaphylaxis,
In 2000, the World Allergy Organization (WAO) published a consensus definition of anaphylaxis as a severe, life-threatening generalized or systemic hypersensitivity reaction.1 The reaction is caused by the release of bioactive mediators from mast cells and basophils.2
The WAO recommends that if the reaction is immunologically mediated— involving IgE, IgG, or immune complex activation of the complement system—the term “allergic anaphylaxis” should be used (examples: peanuts, penicillin, bee venom, blood products, natural rubber latex). If nonimmunological reactions are involved, the organization recommends the term “nonallergic anaphylaxis” (examples: exercise, aspirin and NSAIDs, cold). Anaphylactoid, the older term for nonallergic anaphylaxis, is no longer recommended. Since the signs and symptoms of allergic and nonallergic anaphylaxis may be identical, the presence of 1 of 3 criteria for diagnosis has been suggested (Table 1).
Why one “shock organ” reacts preferentially over another is unknown. Fatalities have been most commonly associated with angioedema of the upper airway, followed by hypotension/
arrhythmias. Since the definition of anaphylaxis has varied from study to study, the prevalence is unknown. Possibly the best estimate is that about 1% of the population have been given an outpatient prescription for epinephrine.3 It is estimated that there are 7 to 10 nonfatal cases of anaphylaxis per 1000 parenteral doses of penicillin (1 fatal reaction per 50,000 doses) and 8 nonfatal cases per 1000 venomous stings from bees, wasps, hornets, and fire ants (40 to 50 deaths in the United States per year).4,5
Once a diagnosis of anaphylaxis is established by a temporal relationship (usually less than 1 hour) between an event (eg, administration of a medication or an x-ray dye, ingestion of a food, or a venomous sting) and the usual clinical manifestations, excellent treatment protocols are available.2
In this article, I suggest 36 ways to avert the largely preventable syndrome of anaphylaxis. An Wang, founder of Wang Laboratories, once said, “Success is more a function of consistent common sense than it is of genius.” Most of the strategies suggested here are little more than that.
1. Always take a complete history of all adverse reactions to any diagnostic or therapeutic agent or to rubber or food.
A classic paper on fatal penicillin reactions states that in 50% of the deaths, no information about previous reactions was available in the medical records. It appears that no question about penicillin allergy was ever posed.4
The standard question “Do you have any drug allergies?” is too vague. Many patients do not consider over-the-counter medications “drugs” and may not be sure what an allergic reaction is. A better question would be “Have you ever had an allergic reaction or a bad reaction to a prescription medicine (such as penicillin), an over-the-counter medication (such as aspirin), a vaccination, an anesthetic, x-ray dye, rubber, blood product, or food?”
2. Don’t bury vital written information about previous reactions.
Prominent display of adverse reactions is particularly important when one physician substituting for another is not as familiar with the patient’s history. In addition to pasting stickers on chart fronts or if possible on the bed of inpatients, I recommend that each chart contain a standardized Adverse Reaction Form listing these facts:
- Date or, if unknown, approximate year of reaction.
- Provoking substance(s).
- Nature of reaction.
- Name of person who is entering the information.
Details such as mild upset stomach from an antibiotic need not be listed. However, when in doubt, record. A future standardized electronic medical record should keep vital information “unearthed.”
3. Always believe the patient who tells you about having had an adverse reaction.
In one study, 70% of patients who died after a penicillin injection had previously received the drug; one-third of them had previously experienced sudden allergic reactions to it.4
In truth, a significant number of patients had told the physician they were allergic to penicillin—but were given it anyway!
4. When a patient tells you about an adverse reaction to a medication, always use an alternative unless a reliable, safe skin test is available to rule out allergy.
A substitute is almost always available for the medication the patient claims caused an adverse reaction. If the offending medication must be used, either seek allergy consultation or use a desensitization protocol (see No. 26). Although hypersensitivity may wane with time, the introduction of even micrograms may cause anaphylaxis in a sensitized patient.
Skin-testing protocols are available only for select IgE-mediated allergic reactions, such as those caused by penicillin. Experience has shown that careful pretesting with penicillin G and benzylpenicilloyl polylysine (PPL) can detect 90% to 95% of persons who have the potential for an anaphylactic reaction. To date, no fatalities have occurred among history-positive, skin test–negative patients who subsequently received penicillin.6 Unfortunately, commercial PPL testing material was removed from the market several years ago; currently, risk assessment by skin testing is available only in research facilities where the reagent can be prepared.
Skin testing with other antibiotics has not been evaluated in as many patients as penicillin has been. Risks associated with administration of other antibiotics to history-positive, skin test–negative patients are unknown.7 If you must use one of these because it is potentially lifesaving and the history suggests allergy, a desensitization protocol (oral route safer than parenteral route) in an ICU is recommended (see No. 26).
5. Know about potential cross-reaction between medications.
The risk of administering a first-generation cephalosporin to a patient with penicillin allergy is not negligible. For higher-generation cephalosporins, the risk is thought to be lower8; however, the package insert for every cephalosporin states caution in use, since “cross-hypersensitivity among β-lactam antibiotics has been clearly documented and may occur in up to 10% of patients with a history of penicillin allergy.” If a cephalosporin is the treatment of choice over antibiotics that do not contain a β-lactam ring, the safest approach is a desensitization protocol (by the oral route if preparations are available). Use a protocol similar to that of penicillin, beginning with 0.05 mg for oral or 0.01 mg for intravenous administration.
NSAIDs pose a high risk in patients who have had an adverse reaction to aspirin, and vice versa. Reactions to aspirin or NSAIDs are not thought to be IgE-mediated; rather, they may be caused by blockade of the cyclooxygenase pathway, because these drugs inhibit prostaglandin synthetase.9 Consequently, there are no skin or in vitro tests to confirm the diagnosis, and giving a test dose is not recommended. Highly successful desensitization protocols are available for patients who have had asthmatic and/or sinusitis reactions to aspirin.10
In patients who are allergic to sulfa, it appears from the literature that using non-arylamine–containing sulfa medications (examples: oral hypoglycemics, diuretics, and NSAIDs such as celecoxib) is safe.8
6. Know how to handle previous adverse reactions to vaccines.
If a patient reports an “allergic” reaction to a vaccine, withhold and follow 1 of these 3 strategies:
- For patients with a future vaccine need, skin test with the vaccine (this requires training and the use of proper skin testing controls) or give the vaccine in a graded-dose protocol and be prepared to treat anaphylaxis.2
- For those with an uncertain need, check antibody levels to see if they are protective. If they are, withhold the vaccine; if not, proceed with the need strategy.
- For those with no need of the vaccine in the future, document the reaction and withhold. Protocols are available for immunotherapy with tetanus toxoid on a need basis; however, these protocols take 10 to 20 weeks to complete.11
7. Know which vaccines contain egg residues and know which ones can be given to egg-allergic patients.
Vaccines against influenza are grown in chick extra-embryonic allantoic fluid; yellow fever in chick embryos; and single-virus rubella, mumps, rubeola, rubella/rubeola, rubella/mumps, rubella/rubeola/ mumps, and rabies in chick embryo fibroblasts.11 Measles-mumps-rubella (MMR) and purified chick embryo rabies vaccines can be given safely, even in egg-allergic patients; however, the safety of other vaccines has not been established.12,13
Before you give vaccines other than MMR or rabies, ask all patients whether they can eat eggs without any adverse reaction and withhold the vaccine if the reaction was anaphylactic. Use of influenza (killed and attenuated live) or yellow fever vaccines in patients with previous nonanaphylactic reactions to eggs is not recommended unless skin testing can be done to assess risk. Use of rabies vaccine in a patient with any previous significant adverse reaction to egg requires immediate allergy consultation. If consultation is not available, proceed with vaccination and be prepared to treat anaphylaxis.
8. Consider the oral rather than the parenteral route when giving antibiotics.
The statistics are frighteningly clear: between 400 and 800 patients per year die of antibiotic-provoked anaphylaxis, and 97% of these deaths are caused by β-lactams. Since penicillin has been in use, the vast majority of fatalities have resulted from parenteral administration.14
9. If you need to give an antibiotic parenterally, consider trying a preliminary oral dose.
The risk of provoking fatal anaphylaxis with oral penicillin is dramatically lower than with parenteral use (about 6 fatalities from orally administered penicillin have been reported). Consider giving the first dose orally and observing the patient for at least 30 minutes before you give the antibiotic parenterally.15
10. Always tell the patient which medication you plan to give just before injecting it.
Saying directly, “I am going to give you penicillin,” can sometimes cause a few synapses to reconnect and previous problems recalled.
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