Allergy and Anaphylaxis During the Postoperative Period

Matthew Sigakis

I. INTRODUCTION

Immediate hypersensitivity reactions to anesthetic and associated agents used during the perioperative period have been reported with increasing frequency. The signs and symptoms of allergic reaction range from slight rash or pruritus to significant hypotension, bronchospasm, and cardiovascular collapse. These may be related to exposures prior to arriving in the postanesthesia care unit (PACU), presenting as a delayed phenomenon, or may result from an initial exposure within the PACU. Although certain sources of exposure are more common perioperatively (Table 27.1), it is important to emphasize that any agent may be the cause.

The diagnosis of allergic reaction or anaphylaxis may be delayed because the presenting signs are often nonspecific. Moreover, recent surgical intervention, anesthetic medications, and underlying comorbidities may complicate the clinical picture. Review of procedural, anesthesia, and PACU medical records is usually helpful in determining a potential allergen exposure.

Identification of allergic reaction or anaphylaxis requires a high index of suspicion and constant vigilance in the PACU, enabling the clinician to intervene promptly, stabilize the patient, address the underlying etiology, and enact a safe plan for continued care and follow-up.

II. DEFINITIONS

The World Allergy Organization (WAO) defines hypersensitivity as “objectively reproducible symptoms or signs initiated by exposure to a defined stimulus at a dose tolerated by normal persons.” The term allergy, more specifically, represents an immune-mediated process. Nonallergic hypersensitivity reactions (also called pseudoallergic reactions) occur with similar symptoms and signs, but without any known immune system involvement.
Immune-mediated allergic reactions are either immediate or delayed.

TABLE 27.1 Perioperative Exposures Most Commonly Associated with Allergic Reaction

Medications

Other Exposures

NMBAs

Antibiotics

Barbiturates

Opioids

Heparin

Protamine

NSAIDs

Oxytocin

Latex

Blood products

Aniline dyes

Contrast

Chlorhexidine

Betadine

Adhesives/tape

NMBAs, neuromuscular blocking agents; NSAIDs, nonsteroidal anti-inflammatory drugs.

There are four classifications:

A. Type I—immediate onset. Due to immunoglobulin E (IgE)-mediated activation of mast cells and basophils.

B. Type II—delayed onset. Due to antibody-mediated cell destruction, immunoglobulin G (IgG) most common.

C. Type III—delayed onset. Due to immune complex (IgG:drug) deposition and complement activation.

D. Type IV—delayed onset. T cell-mediated reaction.

Anaphylaxis traditionally has reflected IgE-mediated reactions, whereas anaphylactoid represented IgE independent reactions. However, because the clinical presentation of these conditions is indistinguishable and the terminology is often confused, the WAO recently discarded these definitions in favor of immunologic anaphylaxis and nonimmunologic anaphylaxis as follows:

A. Immunologic anaphylaxis is immune-mediated; allergic hypersensitivity reaction; mast cell or basophil degranulation involving antibodies or immune complexes.

B. Nonimmunologic anaphylaxis is nonimmune-mediated; nonallergic hypersensitivity reaction; mast cell or basophil degranulation independent of antibodies or immune complexes.

In general, the term anaphylaxis represents an acute process with potentially life-threatening symptoms resulting from the release of mediators from mast cells and basophils.

III. EPIDEMIOLOGY

While the incidence of immunologic and nonimmunologic anaphylaxis has not been specifically studied in the PACU, prior data indicate that approximately 1:10,000 anesthetics will result in an anaphylactic reaction. However, the nonspecific signs of anaphylaxis likely make it underrecognized and underreported. A recent study determined the overall incidence of intraoperative hypersensitivity reactions to be approximately 1:700 patients, and severe hypersensitivity reactions to be approximately 1:4,500 patients.

Perioperative hypersensitivity reactions have been reported to be higher in females, patients with lower body mass index, preexisting medication allergies, and multiple exposures to the same or related antibiotics. There are also genetic associations between human leukocyte antigen alleles and susceptibility to drug hypersensitivity.

IV. PATHOPHYSIOLOGY

A. Immunologic anaphylaxis: Following an initial sensitization, reexposure generates an immune-mediated reaction that results in the release of inflammatory mediators from mast cells and basophils; IgE antibody-mediated reactions being the most rapid in onset. Common perioperative medications/exposures causing immunologic anaphylaxis include neuromuscular blocking drugs, latex, and antibiotics.

B. Nonimmunologic anaphylaxis: Activation of mast cells and basophils occurs without evidence of immunologic involvement and, as a result, may occur on first exposure rather than require a prerequisite exposure for sensitization. Common examples include vancomycin, morphine, and cold temperature exposure. Of note, any agent that can generate a nonimmunologic reaction also has the potential to generate an immune-mediated reaction.

V. CLINICAL SIGNIFICANCE

A. Anaphylaxis

The National Institute of Allergy and Infectious Disease and the Food Allergy and Anaphylaxis Network have established historic and clinical
criteria to help identify cases of anaphylaxis (Table 27.2). These criteria emphasize the rapid onset (minutes to hours) of cutaneous, respiratory, gastrointestinal, or hemodynamic symptoms that may occur after exposure. Additional signs and symptoms reported in the literature include fever, tachycardia, bradycardia, and pulmonary hypertension. Although cutaneous manifestations are often associated with anaphylaxis, they may not be significant and initially go undetected.

TABLE 27.2 Clinical Criteria for Establishing Diagnosis of Anaphylaxis

Any One Below	Subcriteria
Acute onset of illness (minutes to hours) with involvement in skin, mucosal tissue, or both (e.g., generalized hives, pruritus or flushing, swollen lips-tongue-uvula)	At least one: a. Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced peak expiratory flow, hypoxemia) b. Reduced blood pressure (BP) or associated symptoms of end-organ dysfunction (e.g., hypotonia [collapse], syncope, incontinence)
Two or more of the following that occur rapidly after exposure to a likely allergen for that patient (minutes to several hours)	At least two: a. Involvement of the skin-mucosal tissue (e.g., generalized hives, itch-flush, swollen lips-tongue-uvula) b. Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced peak expiratory flow, hypoxemia) c. Reduced BP or associated symptoms (e.g., hypotonia [collapse], syncope, incontinence) d. Persistent gastrointestinal symptoms (e.g., cramps, abdominal pain, vomiting)
Reduced BP after exposure to known allergen for that patient (minutes to several hours)	a. Infants and children: low systolic BP (age specific) or greater than 30% decrease in systolic BP (see symposium report for definitions). b. Adults: systolic BP of less than 90 mm Hg or greater than 30% decrease from that person’s baseline
Adapted from the Second Symposium on the Definition and Management of Anaphylaxis: Summary Report—Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network Symposium, 2006.