52: Allergic Reactions

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CHAPTER 52 Allergic Reactions

James Duke, MD, MBA

1 Review the four types of immune-mediated allergic reactions and their mechanisms

image Type I, or immediate hypersensitivity, is immunoglobulin (Ig) E–mediated hypersensitivity and in its most severe form results in anaphylaxis. Usually there is a previous exposure to the antigen during which IgE is produced and binds to mast cells and basophils. After reexposure the antigen cross-links two IgE receptors, initiating the cascade that ultimately results in release of potent vasodilating mediators. Type I reactions will be discussed in greater detail subsequently.
image Type II reactions involve IgG, IgM, and the complement cascade to mediate cytotoxicity; an example is Goodpasture’s syndrome.
image Type III reactions are the result of immune-complex formation, and their deposition in tissue leads to tissue damage; an example is hypersensitivity pneumonitis.
image Type IV reactions, or delayed hypersensitivity, are mediated by T lymphocytes; the best example is contact dermatitis.

2 What is meant by anaphylaxis?

Anaphylaxis is an unanticipated and severe allergic reaction with numerous clinical manifestations, including the following:

image Hypotension, tachycardia, and cardiovascular collapse
image Bronchospasm
image Cutaneous symptoms, including flushing, urticaria, and angioedema
image Gastrointestinal symptoms, including abdominal pain, nausea and vomiting, and diarrhea

Because surgical patients are under drapes, the usual presenting features intraoperatively are hypotension, tachycardia, and bronchospasm. Since these are not uncommon problems encountered by anesthesiologists, a degree of clinical acumen is necessary to arrive at the diagnosis of anaphylaxis and quickly institute therapy.

3 What is an anaphylactoid reaction?

Although the symptoms are indistinguishable from anaphylaxis, an anaphylactoid reaction is nonimmune mediated. Release of inflammatory mediators from mast cells and basophils results in activation of the complement cascade.

4 What are the common causes of anaphylaxis in the operating room?

About 80% of all anaphylactic reactions are caused by either muscle relaxants (e.g., succinylcholine, rocuronium, and atracurium) or latex exposure, but there are other causes:

image Antibiotics, usually penicillin and other β-lactam antibiotics (cephalosporins) (see Question 6).
image Propofol and thiopental: The incidence of allergic reaction to the most current preparation of propofol is estimated to be 1:60,000 administrations; current evidence also suggests that egg-allergic patients are not at increased risk for allergic reactions. The incidence of anaphylaxis is 1:30,000 administrations and may be caused by the presence of sulfur in the compound. No allergic reactions to methohexital have ever been reported.
image Colloids: Dextran and gelatin have an allergic reaction incidence of about 0.3%. Hetastarch is the safest colloid.
image Morphine and meperidine: More than likely the reaction seen is to the result of nonimmunologic histamine release.
image Aprotinin, heparin, and protamine: Allergic reactions to aprotinin occur in <1% of patients, but reexposure increases the risk. Allergic reactions to unfractionated heparin are rare and to low-molecular-weight heparin are even rarer. The most common reaction to heparin is heparin-induced thrombocytopenia (HIT), which is nonimmunologic in origin. Patients with prior exposure to protamine such as those taking neutral protamine Hagedorn (NPH) insulin have the greatest risk of allergic reaction, about 0.4% to 0.76%.
image Local anesthetics: Allergies to local anesthetics with amide linkages (e.g., bupivacaine, lidocaine, mepivacaine, ropivacaine) are extremely rare. True allergic reactions to local anesthetics with ester linkages (e.g., procaine, chloroprocaine, tetracaine, benzocaine) are also rare and may be caused by a para-aminobenzoic acid metabolite. Methylparaben, a preservative in local anesthetics, may cause allergic reactions.

5 Review the issues concerning allergic reactions to muscle relaxants

About 70% of all intraoperative anaphylactic reactions are associated with relaxants. IgE immunoglobulins are sensitive to the tertiary or quaternary ammonium groups found in these compounds. Since such chemical groups are commonly found in foods, cosmetics, and over-the-counter medications, prior exposure to muscle relaxants is often unnecessary. Succinylcholine is more likely to result in anaphylaxis than nondepolarizing relaxants because its smaller, flexible molecular structure can more easily cross-link mast cell IgE receptors. Benzylisoquinolium relaxants are more likely to result in anaphylaxis than aminosteroid relaxants, and benzylisoquinolium relaxants can also cause nonimmunologic histamine release.

6 Should a penicillin-allergic patient receive cephalosporins?

Authorities disagree on this issue. Although penicillin is the most common cause of anaphylaxis in the general population, interestingly only about 10% to 20% of patients reporting a penicillin reaction have a well-documented allergy, and numerous complaints such as gastrointestinal symptoms or rashes of nonimmunologic origin are labeled allergy. An oft-quoted statistic is that there is an 8% to 10% risk of cross-sensitivity between penicillin and cephalosporins because they share a β-lactam ring, but this is now disputed.

In earlier times this may have been true, possibly because earlier generations of cephalosporins contained trace amounts of penicillin. Some authorities believe cephalosporins are safe to be administered to penicillin-allergic patients as long as these patients have not experienced a prior anaphylactic reaction or have a documented positive skin test for penicillin. However, a 1995 review by Anne et al (1995) found that penicillin-allergic patients were three times as likely to have an anaphylactic reaction to any other drug. Clearly there is a lack of consensus on this issue, and the risks of anaphylaxis must be weighed against the benefits of penicillin therapy. A careful and thorough history of what is meant by penicillin allergy is important in this decision process.

7 What is latex?

Latex is derived from the sap of the Brazilian rubber tree. There are numerous proteins within this product that may produce allergic reactions. Latex products may differ dramatically in the number of allergens detectable within the product. Unfortunately, with the dramatic increase in need for latex products, quantity has been sacrificed for quality. Chemicals from the manufacturing process of commercial latex products may also result in irritant and allergic contact dermatitis.

8 What demographic groups are at risk for latex allergy?

image Historically patients with meningocele, myelomeningocele, and spina bifida were at increased risk for latex allergy because they required chronic bladder catheterization with latex catheters.
image Patients with spinal cord injury and developmental abnormalities of the genitourinary system are also at risk.
image Patients having had multiple operations may develop a latex allergy.
image Atopic individuals (i.e., multiple food allergies, eczema, and asthma) are prone as well.
image Individuals who have problems (rash, itching, edema) with latex products such as condoms, diaphragms, gloves, or dental dams may have severe latex-associated allergic reactions.
image Anyone having had a severe allergic reaction during medical care in the past may have latex hypersensitivity.

9 Has the incidence of latex allergy increased?

In the general population the incidence of latex allergy may be decreasing because of improved recognition of at-risk groups, strategies to avoid latex exposure, and a decrease in latex-containing hospital products. However, in the health-care profession, the incidence is increasing. Standard (previously called universal) precautions have become an everyday practice for health care workers and latex products are an essential feature. The benefit of such practice is to protect these workers from exposure to viral illnesses such as human immunodeficiency virus, hepatitis B and C, and other communicable diseases. Patients are protected from each other as well.

10 How is a latex allergy developed?

There are multiple routes by which individuals can be exposed to allergens, including contact with intact or abraded skin and mucous membranes, inhalation, or exposure to an open vascular tree. Latex gloves are the major source of latex proteins and are the primary factor associated with latex-associated allergic reactions. Powderless gloves reduce latex exposure through the inhalational route.

11 How should an operating room be prepared for a latex-allergic patient?

The cases should be scheduled first since the amount of airborne latex particles is least at the beginning of the day. Nonlatex surgical and anesthesia supplies and nonlatex gloves are essential. Increasingly latex-free medical supplies are the standard for all patients, but it is important to be familiar with supplies at hand since a totally latex-free environment for all cases has yet to be achieved. Ordinarily latex-containing supplies are labeled as such.

12 How should any allergic reaction be treated?

The typical presentation for a severe reaction is in a patient with prior exposure with symptoms developing soon after repeat exposure, although cross-sensitization with commercial products may permit a severe reaction on initial exposure. Respiratory symptoms include edema, especially of mucous membranes and the larynx, bronchospasm, and pulmonary edema. Cardiovascular symptoms include hypotension and tachycardia. Cutaneous manifestations include flushing and hives. These are the manifestations of the most severe, potentially fatal, IgE-mediated reaction known as anaphylaxis. Should a real or likely anaphylactic reaction be recognized, the following recommendations are made:

image Call for help and remove the offending stimulus.
image Limit the use of anesthetic agents as much as possible.
image Complete the procedure as quickly as possible or arrive at a suitable stopping point.
image Administer 100% oxygen.
image Aggressive volume expansion may require many liters of crystalloid.
image Epinephrine 5 to 10 mcg initial bolus, increasing up to 500 mcg if ineffective. Consider epinephrine infusions beginning at 1 mcg/min.
image Antihistamines (histamine-1 receptor blocker): diphenhydramine 25 to 50 mg.
image Antihistamines (histamine-2 receptor blocker): ranitidine 150 mg or cimetidine 400 mg.
image Corticosteroids: hydrocortisone, 1 to 5 mg/kg or methylprednisolone 1000 mg.
image Nebulized albuterol 0.3% for bronchospasm.
image Norepinephrine if epinephrine is insufficient; start about 0.3 mcg/kg/min and increase based on response.
image Vasopressin has also been shown to be effective in doses of 2 to 5 units.

13 Should patients with a prior history of allergic reaction be pretreated with histamine blockers or corticosteroids?

Probably not, because pretreatment may delay recognition of early symptoms until a full-blown reaction manifests, but there is disagreement here.

14 What tests are available to diagnose and characterize a prior allergic reaction? Should patients having a prior anaphylactic reaction be tested?

Serum tryptase, a mast cell protease, will be elevated after both immunologic and nonimmunologic mast cell activation, so is probably of little value. In vitro tests such as the radioallergosorbent test (RAST) detect IgE antibodies and can be performed for specific drugs but are insensitive. In vivo testing such as skin prick and intradermal testing is of variable usefulness because many patients in the general population are also cross-sensitized to many drugs. For instance, over 9% of the general population will have a positive skin prick test to muscle relaxants. In regard to latex, there are so many proteins that usual skin testing may not identify the causative allergen. Furthermore, skin testing can induce a systemic reaction severe enough to require therapy! Many authorities believe that the costs, risks, and limited information gained suggest that testing be undertaken only in unusual circumstances. One instance may be the individual suspected of occupation-related allergies.

15 What are the implications of occupational latex exposure?

Currently about 70% of all allergic reactions are reported in health care workers, and it is estimated that 3% to 12% of this group have developed some degree of latex sensitivity. The majority of allergic reactions are probably caused by inhalational exposure from latex particles adhering to the powder of powdered gloves. Since signs and symptoms may be very nonspecific (puffy eyes, nasal congestion, sneezing, wheezing, coughing, hoarseness), the connection may not be made to an occupational exposure. Workers who develop hand dermatitis or have an atopic history may be at increased risk. It is important to note that, although sensitization may occur at work, severe allergic manifestations may occur while these workers are receiving medical care. The key to the protection of health care workers is to reduce work-related exposure (Stop the Sensitization!). The use of nonpowdered latex or latex-free gloves is probably the most important intervention. Maintaining good skin care is also important, and workers who develop skin rashes might consider visiting an employee health clinic and possible latex sensitivity testing. It is also important not to wear scrub suits home because there are reports of family members developing latex sensitivity by this route.

KEY POINTS: Allergic Reactions image

1. To prevent severe allergic reactions, it is important to identify patients at risk and to take a good history.
2. The major causes of anaphylactic reactions in the operating room are muscle relaxants, followed by latex allergy.
3. Concerning latex allergy, proper preparation of the operating room environment is critical. Schedule patients at risk as first cases. Latex and nonlatex-containing supplies should be clearly identified and the former avoided. Powdered gloves should be avoided.
4. The proper medications needed to adequately treat a reaction should it occur must be at hand. Treat allergic reactions aggressively. Accelerate epinephrine doses if needed.
5. It is important to recognize that health care workers are at increased risk for latex hypersensitivity. Avoid the use of powdered gloves wherever possible and be alert for the development of symptoms that might signify latex allergy.
6. Health care workers with type I latex allergy should have proper allergy identification and always carry an epinephrine Autoinjector device.

Website image

American Society of Anesthesiologists.

http://www.asahq.org/publicationsAndServices/latexallergy.pdf

SUGGESTED READINGS

1. Anne S., Reisman R.E. Risk of administering cephalosporin antibiotics to patients with histories of penicillin allergy. Ann Allergy Asthma Immunol. 1995;74:167-170.

2. Brown S.G. Cardiovascular aspects of anaphylaxis: implications for treatment and diagnosis. Curr Opin Allergy Clin Immunol. 2005;5:359-364.

3. Harboe T., Guttormsen A.B., Irgens A., et al. Anaphylaxis during anesthesia in Norway: a 6-year single-center follow-up study. Anesthesiology. 2005;102:897-903.

4. Hepner D.L., Castells M.C. Anaphylaxis during the perioperative period. Anesth Analg. 2003;97:1381-1395.

5. Kelkar P.S., Li J.T.C. Cephalosporin allergy. N Engl J Med. 2001;345:804-809.

6. Schummer C., Wirsing M., Schummer W. A pivotal role of vasopressin in refractory anaphylactic shock. Anesth Analg. 2008;107:620-625.

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