Version July 2025
INTRODUCTION —
Anaphylaxis is a relatively rare but potentially life-threatening emergency that must be considered and immediately managed when unexpected and significant cardiovascular or respiratory compromise occurs in the perioperative setting. This topic reviews recognition of clinical manifestations and emergency management of suspected anaphylaxis. The etiologies, mechanisms, risk factors, differential diagnosis, incidence, and need for postoperative referral for allergy evaluation are also reviewed here. Emergency treatment of anaphylaxis in other settings is reviewed in a separate topic. (See "Anaphylaxis: Emergency treatment".)
Postoperative evaluation after a presumed anaphylactic reaction is discussed separately, including skin testing to the drugs that potentially cause immunoglobulin E (IgE) mediated reactions and counseling regarding prevention of recurrent reactions. (See "Perioperative anaphylaxis: Allergy evaluation and prevention of recurrent reactions".)
INCIDENCE —
Estimates of the incidence of anaphylaxis during general anesthesia range from 1:350 to 1:20,000, with more recent studies narrowing this range to one case for every 1000 to 10,000 episodes of anesthesia [1-8]. The wide variability in estimates of prevalence and incidence reflects the difficulties in determining the denominator (or the total number of anesthesia cases) and limitations in diagnosing perioperative anaphylaxis.
Perioperative anaphylaxis occurs in children less frequently than in adults (ie, approximately 1 in 37,000 cases), but perioperative clinical manifestations and culprit drugs are similar [9-11].
RISK FACTORS —
Risk factors for perioperative anaphylaxis include:
●History of anaphylaxis, other allergic conditions (eg, asthma, atopic dermatitis, allergic rhinitis, food allergy), or allergic drug reactions. Previous medication reactions nonspecifically increase the possibility of future adverse medication reactions, and multiple previous drug reactions pose a proportionately greater risk [12].
●Patients with multiple past surgeries or other procedures may be at increased risk for reactions to neuromuscular blocking agents (NMBAs) and latex allergies. (See "Latex allergy: Epidemiology, clinical manifestations, and diagnosis", section on 'Diagnosis'.)
●Patients with asthma or chronic obstructive pulmonary disease (COPD) are at greater risk for fatal anaphylaxis from a variety of causes and may be at higher risk for perioperative anaphylaxis, although data are mixed [4,13-15].
●Patients with mast cell disorders, including hereditary alpha-tryptasemia, idiopathic mast cell activation syndrome, monoclonal mast cell activation disorder, and systemic mastocytosis, are at increased risk for clinically significant mast cell mediator release from a variety of stimuli, including the administration of medications that cause nonspecific mast cell activation and physiologic events during surgery (eg, handling of the bowel, extremes of temperature) [16]. Thus, these patients require specific precautionary management prior to procedures or surgery. (See "Indolent and smoldering systemic mastocytosis: Management and prognosis", section on 'Preparation for medical, surgical, and radiologic procedures'.)
Risk factors for a greater likelihood of cardiac arrest and/or death as a result of perioperative anaphylaxis were identified in a 2018 registry as obesity, beta-blocker and/or angiotensin-converting enzyme inhibitor therapy, as well as higher scores on the American Society of Anesthesiologists (ASA) Physical Status Classification system (table 1) [5].
RECOGNITION OF ANAPHYLAXIS
Signs and symptoms — Anaphylaxis is an acute, potentially lethal, multisystem syndrome almost always resulting from the sudden release of mast cell- and basophil-derived mediators into the circulation [17-21]. (See "Pathophysiology of anaphylaxis".)
Anaphylaxis in any setting is diagnosed clinically based on the presence of characteristic signs and symptoms that begin suddenly and progress rapidly in most cases (table 2). There is no definitive test to prove or disprove anaphylaxis. Presentation of anaphylaxis in perioperative patients differs from presentation in patients who are not sedated or under general anesthesia in several ways (table 3) [22-24]:
●Perioperative anaphylaxis is more likely to present as sudden, marked changes in cardiovascular or respiratory parameters [5,25,26]. This is because early or mild symptoms, such as itching or shortness of breath, may go unnoticed if the patient cannot communicate, and skin symptoms may not be visible if the skin is draped or covered.
●Hypotension is often present, but severity may vary from mild hypotension to complete cardiovascular collapse and cardiac arrest. Hypotension is the first detected manifestation in up to 50 percent of cases [5,17]. However, intraoperative hypotension is common for many reasons, as discussed below and in a separate topic. (See 'Other causes of hypotension/shock' below and "Hemodynamic management during anesthesia in adults", section on 'Hypotension: Prevention and treatment'.)
●Bronchospasm may present as a sudden increase in the ventilatory pressure required to inflate the lungs, a decrease in arterial oxygen saturation, or an upsloping pattern in the end-tidal carbon dioxide waveform [27]. Severe bronchospasm and/or cardiac arrest may lead to a flat capnograph [28].
●Laryngeal edema may manifest as difficulty during intubation or as post-extubation stridor and can be associated with facial or tongue edema [29]. However, it may be unrecognized in an intubated patient.
●Tachycardia is a classic sign of anaphylaxis. However, intraoperative tachycardia is common for many reasons, as discussed in a separate topic. (See "Perioperative arrhythmias", section on 'Sinus tachycardia'.)
●Bradycardia may develop later in anaphylaxis if the patient becomes hypoxemic, develops heart block, or experiences coronary hypoperfusion [30,31]. However, intraoperative bradycardia is common for many reasons, as discussed in a separate topic. (See "Perioperative arrhythmias", section on 'Causes of sinus bradycardia'.)
Delayed recognition — Delayed recognition of perioperative anaphylaxis is not unusual; it may be recognized only when dramatic respiratory and hemodynamic changes develop [26]. Immediate management should not be delayed if anaphylaxis is suspected. (See 'Management of suspected anaphylaxis' below.)
Delayed recognition may occur: For example, if the triggering agent was administered or applied by the surgeon (eg, antibiotics in irrigation solutions, topical hemostatic agents, injections of a blue dye for lymph node identification), the anesthesiologist may not immediately make the connection between exposure to the agent and the onset of anaphylaxis (see 'Timing' below). Careful review of the events and temporal sequence preceding the reaction with the entire team may be useful to determine the etiology. (See 'Etiologies' below and 'Referral for allergy evaluation' below.)
Timing — Anaphylaxis due to an IgE-mediated reaction commonly develops within a few minutes following intravenous (IV) administration of the causal agent but potentially can be delayed up to 20 minutes. However, symptoms may manifest later if the culprit agent was administered orally, intramuscularly, or through contact with skin or tissues (eg, latex, chlorhexidine). Aspects of timing that may offer clues to help determine the underlying cause include:
●Soon after induction – Anaphylaxis presenting during the first 30 minutes after induction of anesthesia is more likely due to antibiotics, neuromuscular blocking agents (NMBAs), or hypnotic induction agents because these agents are administered during induction or prior to surgical incision.
●Mid-surgery – Anaphylaxis presenting after the first 30 minutes of anesthetic induction is more likely due to agents administered or used during the maintenance phase of anesthesia, such as latex, blood products, colloid volume expanders, blue dyes, or protamine.
●End of surgery – Anaphylaxis near the end of the surgical procedure can be caused by administration of sugammadex to reverse neuromuscular blockade.
Reactions may also occur after sudden shifts in blood or other fluids, such as removal of a tourniquet, unclamping of blood vessels, or uterine manipulation followed by administration of oxytocin [32-34]. (See "Overview of topical hemostatic agents and tissue adhesives".)
Severity — Perioperative anaphylaxis tends to be more severe and has a higher mortality rate than anaphylaxis occurring in other settings. In a retrospective review of 266 survivors of perioperative anaphylaxis, psychological, cognitive, or physical sequelae were reported in one-third of cases [35]. Estimates of mortality due to perioperative anaphylaxis range from 1.4 to 6 percent, with another 2 percent of patients surviving with anoxic central nervous system injury [15,35-37]. In contrast, fatal anaphylaxis from all causes is estimated to be 0.7 to 2 percent of cases.
Factors that may increase severity in the perioperative setting include IV routes for administration of the triggering agent, delayed recognition of reactions (see 'Delayed recognition' above), and increased patient vulnerability due to coexisting surgical stress, blood loss, or exacerbated vasodilation due to administration of general or neuraxial anesthetic agents.
MANAGEMENT OF SUSPECTED ANAPHYLAXIS
Initial management — Stop administration of or contact with the suspected agent. In the perioperative and intensive care unit settings, first-line treatment of suspected anaphylaxis is the administration of intravenous (IV) epinephrine in 10 to 100 mcg boluses and IV fluid boluses (up to approximately 25 to 50 mL/kg) (table 4). If systolic blood pressure (BP) is <50 mmHg or undetectable, then advanced cardiac life support (ACLS) protocol with chest/cardiac compressions is initiated. (See "Intraoperative advanced cardiac life support (ACLS)".)
If signs of anaphylaxis persist despite epinephrine boluses and fluid administration, an IV infusion of epinephrine should be initiated at initial doses of 2 to 10 mcg/minute and titrated to effect. These recommendations are consistent with the 2024 guidelines for emergency treatment of perioperative anaphylaxis developed by the Resuscitation Council of the United Kingdom [38] and other previously published national or international consensus recommendations [39,40].
In perioperative and critical care settings, these initial and subsequent treatments are administered via an IV route, allowing titration to specific effects (table 4). In most other settings without vascular access, clinicians give epinephrine via intramuscular or other routes to treat suspected anaphylaxis. Data supporting epinephrine as the first-line treatment for anaphylaxis are discussed in a separate topic. (See "Anaphylaxis: Emergency treatment", section on 'Epinephrine'.)
ACLS protocols should be started if systolic BP is <50 mmHg despite initial administration of IV epinephrine and IV fluids [28,38]. If hypotension is refractory to epinephrine infusion, then vasopressin or norepinephrine may be titrated to effect (table 5). Additional vascular access may be necessary. Also, fluid administration is continued up to 50 mL/kg for refractory hypotension. Further hemodynamic monitoring is implemented as soon as feasible after the first 2 liters of fluid resuscitation have been administered. Methylene blue (1.5 to 2 mg/kg slow bolus with 0.5 to 1.5 mg/kg/hour) has been studied for vasoplegia refractory to pressors, although data are limited [41,42].
For patients with persistent bronchospasm, albuterol 4 to 8 puffs is also administered via the endotracheal tube (ETT). Alternatively, 2.5 mg albuterol in 2.5 mL of saline may be nebulized for administration via the ETT or continuous 60-minute nebulization with 10 mg albuterol in 10 mL of saline.
After initial hemodynamic resuscitation, subsequent therapy typically includes administration of a systemic glucocorticoids (eg, methylprednisolone 125 mg IV or hydrocortisone 100 mg IV) and antihistamines (eg, an H1 antihistamine such as diphenhydramine 50 mg IV and an H2 antihistamine such as famotidine 20 mg IV), particularly if urticaria is present. However, there is no evidence that these treatments improve outcome or diminish the occurrence of biphasic anaphylaxis. If these adjunct therapies are used, they should be given as a single dose or quickly discontinued so that side effects are minimized.
Decisions regarding proceeding with surgery — Decisions regarding whether to proceed with surgery following a suspected anaphylactic reaction are individualized and depend on severity of the reaction, cardiopulmonary stability of the patient, and urgency of the procedural intervention. Ultimately, clinicians must use clinical judgment to determine the most sensible course of action.
In one retrospective analysis, proceeding with surgery was safe after anaphylactic reactions that were limited to cutaneous signs and/or vital sign changes that were not life threatening (ie, grade 1 or 2 reactions). After anaphylaxis with profound hypotension or severe bronchospasm (grade 3), the risk of adverse events attributable to the reaction was higher, but surgical outcomes did not differ if surgery was continued or abandoned [43]. In this study, surgical procedures were frequently abandoned after grade 4 reactions (associated with cardiac arrest and/or inability to ventilate). However, even in this situation, there was no evidence of further harm as a result of proceeding with emergency or partially completed major surgery.
Laboratory tests at the time of the reaction — A red-top tube of blood should be collected as soon as possible after the onset of signs or symptoms of anaphylaxis for analysis of serum tryptase, a mediator released nearly exclusively by mast cells and basophils [44]. Elevations in tryptase aid in distinguishing anaphylaxis from other perioperative causes of hemodynamic instability and/or respiratory distress [45,46]. Serum tryptase has a half-life of approximately two hours; thus, collection within 30 minutes to three hours of the event is optimal. In some cases, if massive mast cell activation occurs, increases may be detectable for longer.
Serum that was collected at the time of the reaction for other reasons can sometimes be retrieved at a later time and assayed. Tryptase is stable in frozen serum for up to one year. Levels of tryptase can increase dramatically after death due to nonspecific mediator release during cell death. For postmortem samples, blood should be collected from the femoral artery or vein, not the heart. Interpretation is discussed elsewhere. (See "Laboratory tests to support the clinical diagnosis of anaphylaxis", section on 'Fatal anaphylaxis'.)
Assays of other mast cell and basophil products, such as serum and urinary histamine, histamine metabolites, and prostaglandins, are generally of limited value but are collected in some centers [6,47]. (See "Laboratory tests to support the clinical diagnosis of anaphylaxis".)
Results of available assays are considered during subsequent allergy evaluation, as noted below and reviewed separately. (See 'Referral for allergy evaluation' below and "Perioperative anaphylaxis: Allergy evaluation and prevention of recurrent reactions".)
DIFFERENTIAL DIAGNOSIS —
The differential diagnosis of an allergic or anaphylactic reaction during or following general anesthesia includes a broad list of reactions and physiologic events [3,48-51]. Tryptase levels should be normal in all of these other disorders.
However, even when the diagnosis of anaphylaxis is uncertain, other causes of severe reactions with similar symptoms (eg, respiratory or airway compromise, hypotension/shock, angioedema, urticaria) are also treated with intravenous (IV) epinephrine, IV fluid boluses, and advanced cardiac life support (ACLS) with chest/cardiac compressions if systolic blood pressure (BP) is <50 mmHg or undetectable (table 4). These lifesaving treatment interventions should not be delayed.
Other causes of respiratory or airway compromise — Other perioperative causes of airway or respiratory distress are common during surgery and anesthesia, as listed below and discussed separately (see "Assessment of respiratory distress in the mechanically ventilated patient"):
●Acute bronchospasm in a patient known to have asthma or chronic obstructive pulmonary disease (COPD) (see "Anesthesia for adult patients with asthma", section on 'Intraoperative bronchospasm')
●Aspiration
●Endotracheal tube malposition
●Inadequate depth of anesthesia
●Malignant hyperthermia (succinylcholine) (see "Malignant hyperthermia: Diagnosis and management of acute crisis", section on 'Diagnosis')
●Myotonias and masseter spasm (succinylcholine) (see "Neuromuscular blocking agents (NMBAs) for rapid sequence intubation in adults for emergency medicine and critical care", section on 'Trismus')
●Post-extubation stridor (see "Postoperative airway and pulmonary complications in adults: Management following initial stabilization", section on 'Immediate, potentially life-threatening emergencies')
●Pulmonary edema
●Pulmonary embolus (see "Clinical presentation and diagnostic evaluation of the nonpregnant adult with suspected acute pulmonary embolism")
●Tension pneumothorax (see "Clinical presentation and diagnosis of pneumothorax", section on 'Clinical presentation')
●Transfusion-related acute lung injury (TRALI) (see "Transfusion-related acute lung injury (TRALI)", section on 'Clinical presentation')
Other causes of hypotension/shock — Other perioperative causes of hypotension are common during general anesthesia, as listed below and discussed separately (see "Hemodynamic management during anesthesia in adults", section on 'Hypotension: Prevention and treatment'):
●Amniotic fluid embolus
●Arrhythmias
●Bone cement implantation syndrome (see "Complications of total hip arthroplasty", section on 'Bone cement implantation syndrome')
●Cardiac tamponade
●Cardiogenic shock
●Hemorrhage
●Hyperkalemia
●Overdose of vasoactive drugs
●Partial sympathectomy from spinal/epidural anesthesia
●Pulmonary embolus
●Sepsis
●Vasovagal reaction
●Venous air embolism (see "Air embolism", section on 'Clinical features')
Other causes of angioedema
●Hereditary or acquired C1 esterase inhibitor deficiency (see "Hereditary angioedema (due to C1 inhibitor deficiency): Acute treatment of angioedema attacks")
●Soft tissue swelling due to difficult intubation (see "Complications of airway management in adults", section on 'Soft tissue injury')
●Treatment with angiotensin-converting enzyme inhibitors (see "An overview of angioedema: Pathogenesis and causes", section on 'Causes')
Other causes of urticaria — Cold urticaria can occasionally be mistaken for perioperative anaphylaxis or a drug reaction. Cold urticaria can progress to anaphylaxis as well. The diagnosis can usually be excluded by the negative results of an ice cube challenge, except for familial cold urticaria associated with cryopyrin dysfunction [52]. (See "Cold urticaria".)
Opioids, particularly following IV administration, often trigger cutaneous mast cell degranulation directly and cause urticaria, usually without systemic manifestations of anaphylaxis. Nonsteroidal antiinflammatory drugs (NSAIDs) also augment cutaneous mast cell degranulation and accentuate urticaria. Much less commonly, anaphylaxis can result from opioids or NSAIDs. (See 'Less common agents' below.)
ETIOLOGIES —
The best longitudinal data about perioperative anaphylaxis are derived from a series of multicenter French surveys, which began in the mid-1990s and have continued to the present [13,53-55]. The causes of perioperative anaphylaxis can be divided into two groups: more common and less common (table 6). Allergy evaluation and skin testing for each of these agents are discussed separately. (See "Perioperative anaphylaxis: Allergy evaluation and prevention of recurrent reactions", section on 'Evaluation'.)
More common agents — Among cases in which a trigger could be identified, the more common causes in rank order were [3,5,13,32,55-61]:
●Antibiotics, especially penicillins and cephalosporins (most common cause in several American, United Kingdom, and some European studies)
●Neuromuscular blocking agents (NMBAs; most common cause in many European studies)
●Blue dyes (also known as vital dyes, including isosulfan blue, patent blue V, methylene blue)
●Blood products
These same medications have been implicated in studies around the world, although the rank order may differ.
Less common agents — In the French studies mentioned previously, the following groups of agents were implicated in less than 10 to 15 percent of reactions [13]:
●Colloids and plasma volume expanders, especially those containing gelatin
●Latex
●Protamine
●Other agents, including anesthetics such as sedative hypnotics and opioids, radiocontrast, nonsteroidal antiinflammatory drugs (NSAIDs), povidone, sterilizing agents such as ethylene oxide and ortho-phthalaldehyde (Cidex OPA [sample brand name]), streptokinase or urokinase, heparin, other gelatin-containing products
A more detailed discussion of potential etiologies is found separately. (See "Perioperative anaphylaxis: Allergy evaluation and prevention of recurrent reactions".)
Role of alpha-gal allergy — Some cases of anaphylaxis attributed to animal-derived products, such as gelatin-based colloids [62], bovine or porcine heart valves [63], heparin [64,65], and hemostatic agents derived from gelatin (eg, Gelfoam powders, sponges, etc), may be caused by allergy to the carbohydrate moiety galactose-alpha-1,3-galactose (also called alpha-gal) [66], although there are other potential allergens in these products [67]. Reactions range in severity from transient urticaria to anaphylaxis and may be delayed by several hours [65]. Alpha-gal allergy is discussed separately in more detail. (See "Allergy to meats", section on 'Alpha-gal'.)
●When to suspect – Understanding of the role of alpha-gal versus other allergens in suspected allergic reactions is evolving. Alpha-gal allergy occurs more commonly in the Southeastern United States, as well as specific areas of Europe, Asia, and Australia, although prevalence of this allergy is uncertain and varies regionally and seasonally. Alpha-gal allergy may be suspected in patients with:
•Delayed allergic reactions following ingestion of mammalian meats (eg, beef, pork, lamb)
•Prior, immediate reaction to IV cetuximab
•A non-B blood group
•Frequent outdoor exposure to ticks in high-risk environments (eg, hunting, hiking, camping, forestry workers)
A positive history would not necessarily preclude the use of animal-derived products during the surgical procedure, but the surgical team should have increased vigilance to avoid delayed recognition of a reaction. (See 'Delayed recognition' above.)
●Prophylactic measures for high-risk patients – Prescreening for a positive alpha-gel test in patients who may be at risk has been suggested for patients scheduled for cardiac surgery, particularly if high-dose, porcine- or bovine-derived unfractionated heparin will be required [64,65,67-69]. Although premedication with H1/H2 antihistamines, glucocorticoids, and/or leukotriene modifiers is generally ineffective for IgE-mediated reactions, it may be beneficial in subjects with mixed mechanisms of reactions, severe asthma, or mast cell disorders. (See 'Mechanisms of anaphylaxis' below.)
Consistent with this, some experts advocate the use of prophylactic premedications in patients with known alpha-gal allergy or high alpha-gal-specific IgE levels undergoing high-risk cardiac surgery.
MECHANISMS OF ANAPHYLAXIS —
The various mechanisms leading to activation of mast cells and basophils are increasingly grouped together under the term "anaphylaxis" because the initial management of these reactions is the same, regardless of the trigger or mechanism involved, and the clinical severity of the reactions may be similar [17,18]. In addition, several of the agents commonly implicated in perioperative anaphylaxis (eg, neuromuscular blocking agents [NMBAs]) are capable of causing reactions through more than one mechanism (table 7 and table 8) [70]:
●IgE-mediated mechanisms – IgE-mediated mechanisms account for approximately 60 percent of perioperative anaphylaxis [36]. IgE-mediated anaphylaxis is generally more severe than non-IgE-mediated anaphylaxis [13,71], although both types can be fatal. Immediate-type skin testing methods (ie, prick-puncture and intradermal techniques) are only useful in evaluating IgE-mediated reactions. IgE-mediated reactions are not prevented by premedication with glucocorticoids or antihistamines. Some IgE-mediated reactions are amenable to desensitization techniques if repeat anesthesia is required, but this can be difficult to coordinate.
●Non-IgE-dependent immunologic mechanisms – Formerly called "anaphylactoid"; included in this category are reactions mediated by immunoglobulin G (IgG) or immunoglobulin M (IgM) antibodies or by antigen-antibody complexes and complement. Other mechanisms for immediate reactions that can resemble anaphylaxis include cytokine release syndrome [72]. This type of reaction may feature fever, rigors, or pain and is characterized by elevated levels of interleukin (IL) 6. This is particularly associated with reactions to monoclonal antibody and chemotherapy infusions (not relevant to anesthesia or surgery), but blood transfusions may rarely trigger IL-6 release [73]. IL-6 blood levels is a commercially available assay.
●Nonimmunologic mechanisms – Some medications and other substances can cause direct release of histamine and other mediators from mast cells and basophils [24,74-77]. Nonimmunologic perioperative reactions may be mitigated with subsequent exposure to the culprit by pretreatment with antihistamine and glucocorticoid therapy. (See "Perioperative anaphylaxis: Allergy evaluation and prevention of recurrent reactions", section on 'General precautions'.)
REFERRAL FOR ALLERGY EVALUATION
Whom to refer — All patients with suspected perioperative anaphylaxis should be referred for evaluation by an allergist to identify the likely triggering agent and provide the patient and other clinicians with counseling regarding future precautions [78-80]. In contrast, transient, limited flushing or localized erythema (eg, following vancomycin infusion) is unlikely to represent a significant hypersensitivity reaction and does not need evaluation [3].
The evaluation of perioperative anaphylaxis is complicated, and not all allergy specialists are experienced or comfortable performing it. We suggest referral to a center with specific expertise whenever possible.
Timing of referral — Referrals to an allergy specialist should occur as soon as possible after the reaction, especially if more surgery will likely be needed in the near future (eg, trauma patients). In centers with an allergy consultation service, the referral can take place immediately. Allergy skin testing is generally deferred for four to six weeks after a significant reaction because the skin can become transiently hyporeactive, but each case requires discussion, data collection, and planning before skin testing in advance of testing. In reality, allergy evaluation takes place after the patient has recovered fully in most cases. Allergy skin testing performed promptly in the weeks to months after a reaction is most likely to identify a culprit drug, but testing performed even years after a reaction can be informative. Thus, for patients reporting perioperative anaphylaxis years earlier, an evaluation may still be able to provide some useful information, although the sensitivity of testing will be lower. The impact of timing on skin testing results is discussed in greater detail separately. (See "Perioperative anaphylaxis: Allergy evaluation and prevention of recurrent reactions", section on 'Timing of skin testing'.)
Critical communication among specialties — Ideally, the anesthesiologist should speak with the allergy/immunology consultant to discuss questions about the timing of events, details of the procedure, pharmacologic therapy before and during anesthesia, prior anesthetic events and agents used, expected timing of future surgery, and anesthetic options in the facility. Often this information is difficult for the consultant to obtain in the absence of direct communication.
To maximize the likelihood of identifying the culprit allergen, the referring anesthesiologist and/or surgeon should provide the following specific information to the allergist about the surgery:
●A detailed description of the event, including all signs and symptoms.
●Copies of anesthesia records and surgical reports.
●The timing of anaphylaxis onset relative to the administration of drugs, blood products, blue dyes, or other agents or to the performance of procedures (ie, what was happening during the surgery, just before the reaction was detected).
●The results of serum tryptase levels drawn near the time of the reaction, if available (see 'Laboratory tests at the time of the reaction' above). Elevations in serum tryptase are most often detected in anaphylaxis cases involving hypotension. The equation 1.2 x baseline tryptase + 2 ng/mL is used to calculate the level indicative of mast cell activation. However, not all episodes of anaphylaxis result in elevations in tryptase, so a normal tryptase does not exclude anaphylaxis.
●Whether latex was used (eg, latex gloves, catheters).
●Whether surgical instruments were used in the procedure (because disinfectant chemicals can be allergens).
●Any type of sterilizing agent (eg, ethylene oxide) used for instruments and disinfectants (especially chlorhexidine), local anesthetic sprays/gels, dyes, or cements used during the surgery.
●A description of the composition of any arterial, venous, and urinary catheters and stents used and if chlorhexidine was associated with the devices.
●Whether and when any noncrystalloid volume expanders, gelatin (not used in the United States), or hemostatic agents were used.
●Alternative anesthetic agents available for use in the facility.
Skin testing is the major tool utilized by allergists/immunologists to identify the likely culprit drug and/or to recommend alternative agents. Although the positive predictive value or likelihood ratio of positive skin tests for agents or drugs other than penicillin is not defined, this approach has proven successful in a majority of cases. One study of 70 patients showed that assessment with skin testing in a specialty clinic resulted in 67 patients undergoing repeat anesthesia without adverse events [81]. The few cases of repeat anaphylaxis were attributed to either limitations in the historical information provided to the allergy consultant or the presence of undetected mast cell disorders. This highlights the importance of providing a detailed description of the events and timing of drug administration to the consulting allergist. Ideally, the anesthesiologist should also be prepared to provide small aliquots of anesthetic drugs to facilitate testing as these agents are not readily available to other clinicians. However, the logistics of providing these regulated materials is often a challenge. (See "Perioperative anaphylaxis: Allergy evaluation and prevention of recurrent reactions", section on 'Skin testing'.)
SOCIETY GUIDELINE LINKS —
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Perioperative anaphylaxis".)
SUMMARY AND RECOMMENDATIONS
●Incidence and risk factors – Estimates of the incidence of perioperative anaphylaxis range from one case for every 1000 to 10,000 episodes of anesthesia. Risk factors include a history of anaphylaxis, other allergic conditions (eg, asthma, atopic dermatitis, allergic rhinitis, food allergy), allergic drug reactions, mast cell disorders, and multiple past surgical procedures. (See 'Incidence' above and 'Risk factors' above.)
●Recognition of anaphylaxis:
•Presentation – Anaphylaxis is diagnosed clinically based on the presence of characteristic signs and symptoms that begin suddenly and progress rapidly in most cases (table 2). Presentation of anaphylaxis in perioperative patients differs from other settings, as noted in the table (table 3). (See 'Signs and symptoms' above.)
•Delayed recognition – Perioperative anaphylaxis may be recognized only when dramatic respiratory and hemodynamic changes develop. (See 'Delayed recognition' above.)
•Timing – Anaphylaxis due to an immunoglobulin E (IgE) mediated reaction usually develops a few minutes following intravenous (IV) administration of the causal agent. However, symptoms may manifest later if the trigger was administered orally, intramuscularly, or through contact with skin or tissues. (See 'Timing' above.)
•Severity – Perioperative anaphylaxis tends to be more severe, with a higher mortality rate than anaphylaxis occurring in other settings. Factors may include IV routes of administration of the triggering agent, delayed recognition of reactions, and increased patient vulnerability due to coexisting surgical stress, blood loss, or vasodilation due to administration of general or neuraxial anesthetic agents. (See 'Severity' above.)
●Management:
•Epinephrine for initial management – Stop administration of the suspected agent. Patients with suspected perioperative anaphylaxis require immediate administration of epinephrine. In the perioperative setting, we give IV epinephrine in 10 to 100 mcg IV boluses that may be repeated or administered in escalating doses every one to two minutes (table 4). We also administer IV fluid boluses (up to approximately 25 to 50 mL/kg) to treat hypotension/shock. If systolic blood pressure (BP) is <50 mmHg or undetectable, initiate advanced cardiac life support (ACLS) protocol including chest/cardiac compressions. (See 'Initial management' above.)
•Persistent hypotension – For ongoing hypotension, we suggest an IV epinephrine infusion, rather than repeated bolus doses of epinephrine or other vasopressors (Grade 2C). We give 2 to 10 mcg/minute titrated to effect. If hypotension is refractory to epinephrine infusion, vasopressin or norepinephrine may be administered and titrated to effect. Also, fluid administration is continued up to 50 mL/kg for refractory hypotension.
•Persistent bronchospasm – For persistent bronchospasm, we also administer albuterol via puffs or in nebulized saline via the endotracheal tube.
•Adjunctive therapies – After initial resuscitation and management, additional adjunctive therapies are often given (eg, methylprednisolone 125 mg IV or hydrocortisone 100 mg IV) and antihistamines (eg, an H1 antihistamine such as diphenhydramine 50 mg IV and an H2 antihistamine such as famotidine 20 mg IV), but there is no evidence that they prevent biphasic reactions or improve outcomes.
●Decisions regarding the surgical procedure – Decisions regarding whether to proceed with surgery following suspected anaphylaxis are individualized and depend on the severity of the reaction, cardiopulmonary stability of the patient, and urgency of the surgical procedure. (See 'Decisions regarding proceeding with surgery' above.)
●Laboratory testing – Blood should be collected for analysis of serum tryptase (in a red-top tube, with a recommended minimum of 1 mL) as soon as possible after the event (within 30 minutes to three hours). (See 'Laboratory tests at the time of the reaction' above.)
●Differential diagnosis – Other causes of severe reactions may present with similar symptoms (eg, respiratory or airway compromise, hypotension/shock, angioedema, urticaria). However, each of these entities is treated similarly (administration of IV epinephrine, fluid boluses, and ACLS if systolic BP is <50 mmHg (table 4)); thus, treatment should not be delayed. (See 'Differential diagnosis' above.)
●Etiologies – The more common, identifiable causes of perioperative anaphylaxis are antibiotics, neuromuscular blocking agents (NMBAs), chlorhexidine, and blue dyes used in lymph node mapping. Other agents frequently used in the perioperative setting may cause anaphylaxis, including blood products, colloids, protamine, latex, anesthetics and adjunct agents such as sugammadex, and agents that trigger alpha-gal allergy (table 6). (See 'Etiologies' above and "Perioperative anaphylaxis: Allergy evaluation and prevention of recurrent reactions".)
●Referral to an allergist – After a suspected perioperative anaphylactic event, evaluation by an allergist is indicated whenever possible to identify the likely triggering agent and provide advice regarding future precautions. Clinical history and perioperative records are reviewed, serum tryptase levels are evaluated compared with baseline levels, and skin testing is performed, if relevant, to identify the likely culprit agent. (See 'Referral for allergy evaluation' above.)
