INTRODUCTION — Patients undergoing general anesthesia and surgery can experience complex physiologic changes, which may complicate recognition of an allergic reaction.
The prevalence, etiology, risk factors, clinical manifestations, and acute diagnosis of anaphylaxis during general anesthesia will be reviewed here. The evaluation of a patient who has experienced perioperative anaphylaxis, skin testing to the drugs that cause immunoglobulin E (IgE)-mediated reactions, and prevention of recurrent reactions, as well as the treatment of anaphylaxis from any cause, are discussed separately. (See "Perioperative anaphylaxis: Evaluation and prevention of recurrent reactions" and "Anaphylaxis: Emergency treatment".)
INCIDENCE — The incidence of anaphylaxis during general anesthesia is 1:10,000 to 1:20,000 [1-5]. The wide variability in estimates of prevalence and incidence reflects the difficulties in determining the denominator (or the total number of anesthesia cases), as well as limitations in diagnosing perianesthetic anaphylaxis. Perioperative anaphylaxis occurs equally in prepubertal girls and boys but is more common in adult women than men [3].
MECHANISMS OF ANAPHYLAXIS — 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 [6-10]. (See "Pathophysiology of anaphylaxis".)
In this review (and increasingly in the literature), the term "anaphylaxis" applies to all of the following mechanisms of acute reactions (table 1) [11]:
●IgE-dependent mechanisms, which account for approximately 60 percent of perioperative anaphylaxis [12].
●Non-IgE-dependent immunologic mechanisms (formerly called anaphylactoid); included in this category are reactions mediated by IgG or IgM antibodies or by antigen:antibody complexes and complement.
●Nonimmunologic mechanisms (formerly called anaphylactoid) involving direct release of histamine and other mediators from mast cells and basophils [13-17].
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 [6,7]. In addition, several of the agents that are commonly implicated in perioperative anaphylaxis, such as neuromuscular-blocking agents, are capable of causing reactions through more than one mechanism (table 2).
Despite the similarities, there are important differences in the evaluation, prevention, and prognosis of the various types of reactions (table 1):
●Immediate-type skin testing methods (ie, prick-puncture and intradermal techniques) are only useful in evaluating IgE-mediated reactions.
●The severity of IgE-mediated reactions may increase with subsequent administration of the causal agent, while the severity of repeat reactions arising from other mechanisms, particularly nonimmunologic mechanisms, usually remains similar.
●The severity of anaphylaxis associated with specific IgE to the culprit agent is often more severe than anaphylaxis in which specific IgE cannot be identified [3,18].
●Some IgE-mediated reactions are amenable to desensitization techniques if retreatment is required.
●Reactions to radiocontrast media, usually mediated by a nonimmunologic mechanism, can be reduced in frequency or intensity by use of iso-osmolar contrast and pretreatment with antihistamines and glucocorticoids.
ETIOLOGIES — The most common identifiable causes of perioperative anaphylaxis are antibiotics, blood products, chlorhexidine, neuromuscular-blocking agents (NMBAs), and the NMBA reversal agent sugammadex. However, there is a much longer list of agents that are implicated less commonly and include hypnotic induction agents, opioids, colloids, and latex. In a significant number of cases, no specific trigger can be identified.
The best 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 [3,19-21]. The causes of perioperative anaphylaxis can be divided into two groups (ie, more common and less common).
More common — Among cases in which a trigger could be identified, the more common causes were [2,3,21-26]:
●Antibiotics, especially penicillins and cephalosporins (most common cause in several American and some European studies)
●NMBAs (most common cause in many European studies)
These same medications have been implicated in studies around the world, although the rank order may differ. Specifically, antibiotics appear to be the most common cause of perioperative anaphylaxis in the United States, while NMBAs are the leading cause in most European studies [21,27,28].
Antibiotics — Antibiotics, administered before, during, or immediately after anesthesia, were responsible for 12 to 15 percent of identifiable triggers in the French studies [3,22]. In an American series, antibiotics accounted for 50 percent of IgE-mediated reactions [28,29]. A German series of 107 patients reported 24 of the 53 identified culprit drugs to be antibiotics [18]. A prospective United Kingdom registry collected 286 cases of perioperative anaphylaxis over 12 months [25]. Among the 199 cases with a defined probable cause, 47 percent were attributed to antibiotics.
Beta-lactam antibiotics (specifically penicillins and cephalosporins), which cause IgE-mediated anaphylaxis, and vancomycin, which usually causes reactions due to direct histamine release from mast cells, are the most common offenders [2,22,30-32]. Quinolones are infrequently but increasingly incriminated. Hypersensitivity reactions to these agents are reviewed elsewhere. (See "Penicillin allergy: Immediate reactions" and "Cephalosporin hypersensitivity: Clinical manifestations and diagnosis" and "Vancomycin hypersensitivity".)
Neuromuscular-blocking agents — Fifty to 70 percent of anaphylaxis cases related to anesthesia were due to NMBAs (also called muscle relaxants), making these agents the most common identifiable trigger in the French surveys [2,3,21,22,33]. NMBAs can cause anaphylaxis through both IgE-mediated and nonimmunologic, direct mast cell activation (table 2) [17,34-36]. Commonly implicated agents include rocuronium, succinylcholine (also known as suxamethonium), atracurium, pancuronium, tubocurarine (no longer available in the United States and Canada but used elsewhere), and vecuronium, although this list may largely reflect the frequency with which these agents are used [2,22]. In the 2018 United Kingdom prospective registry, succinylcholine was the most common cause of anaphylaxis among the NMBAs. The reaction rate was equal among the nondepolarizing agents, with the occurrence reflecting the frequency of use [25]. The data also show that succinylcholine more commonly causes bronchospasm, whereas atracurium presents primarily with hypotension. Thus, there may be subtle differences in the pattern of anaphylaxis based on the culprit NMBA.
Allergy to NMBAs is more common in women than men, with three of four reactions occurring in females [3,33]. IgE sensitization is believed due to cross-reactive tertiary or quaternary ammonium groups found in both NMBAs and a variety of topical cosmetics and personal products, as well as certain over-the-counter cough remedies (ie, pholcodine, commonly used in France, Norway, and other European countries) [37-40]. These ammonium groups are highly immunoreactive, multivalent epitopes, which can induce specific IgE antibodies. Sensitization through exposure to nonmedication agents may explain why allergic reactions to NMBAs can occasionally occur upon initial exposure.
There may be a specific receptor on mast cells activated by NMBAs as well as other drugs, such as fluoroquinolones [16]. This receptor is designated MRGPRX2 and has the capability of binding to a variety of ligands, which could activate mast cells with a specific, immune-like response. In addition to NMBAs, these activators include substance P and peptidergic drugs, such as icatibant, used to treat hereditary angioedema by blocking the bradykinin receptor. A specific inhibitor of MRGPRX2 in animal models has blocked IgE-independent anaphylaxis.
Reactions resulting from IgE-mediated allergy are less common, although usually more severe, than reactions due to direct mast cell activation. Histamine release may be more prominent with certain NMBAs, such as tubocurarine, mivacurium, atracurium, and rapacuronium. Rapacuronium was withdrawn from the United States market, because it was implicated in high rates of severe bronchospasm (without other symptoms) [41].
It is possible that the prevalence of sensitization to NMBAs is overestimated to some degree. The high rate of reactions attributed to NMBAs in some studies may be based on skin testing results, and these drugs can cause nonspecific mast cell release, causing false-positives skin test results [40]. Skin testing to NMBAs and cross-reactivity among these drugs are discussed separately. (See "Perioperative anaphylaxis: Evaluation and prevention of recurrent reactions", section on 'Neuromuscular-blocking agents'.)
Chlorhexidine — Chlorhexidine is a topical antiseptic and surgical scrub that is increasingly implicated in perioperative anaphylaxis [23,42-50], accounting for 9 percent of the cases reported in the 2018 United Kingdom prospective registry [25]. Reported culprit products include antiseptic solutions applied to surgical fields (especially mucosal surfaces) and urethral lubricants. Some central venous catheter tips are impregnated with chlorhexidine. This compound is found in nonmedical settings in toothpastes, antiseptic mouthwashes, bathing solutions, and lozenges. Patients may become sensitized through exposure to such products.
Sugammadex — Sugammadex is a highly charged cyclodextrin that rapidly encapsulates and inactivates steroidal NMBAs (ie, rocuronium or vecuronium) [51-56]. It forms a high affinity complex with the NMBA in plasma, thereby reducing the amount of the NMBA available to bind to nicotinic receptors in the neuromuscular junction, which results in rapid reversal of neuromuscular blockade. (See "Clinical use of neuromuscular blocking agents in anesthesia", section on 'Sugammadex'.)
Since its introduction in the European Union in 2008 and subsequently in other countries, sugammadex has been increasingly implicated as a cause of perioperative anaphylaxis [53]. A 2014 systematic review estimated that anaphylactic reactions occur in 1:3500 to 1:20,000 exposures, while a large 2018 series from the United Kingdom reported a lower rate of 1 in 64,000 exposures [57,58]. A Japanese study estimated the rate of anaphylaxis to be similar to that caused by NMBAs, although this may be partly explained by relatively widespread use of sugammadex in that country [51]. Possible mechanisms for these reactions are discussed separately. (See "Perioperative anaphylaxis: Evaluation and prevention of recurrent reactions", section on 'Sugammadex'.)
Hypersensitivity reactions to sugammadex typically appear rapidly after intravenous administration (ie, usually within one minute but sometimes up to several minutes later) and can occur with first-time administration. Risk factors have not been identified. Reactions can involve clinically significant airway edema and bronchospasm, and if this develops after extubation, reintubation may be required [59-61]. Repeat administration of sugammadex following a suspected reaction is contraindicated.
Less common — In the French studies mentioned previously, the following groups of agents were implicated in less than 10 to 15 percent of reactions [3]:
●Colloids and plasma volume expanders
●Hypnotic induction agents
●Opioids
●Latex
●Other agents
Colloids and plasma expanders — Colloids and plasma expanders, such as dextran or hetastarch (hydroxyethyl starch [HES]), accounted for approximately 3 percent of identifiable causes of perioperative anaphylaxis in large series [2,22,62]. These agents are capable of causing both IgE-mediated and non-IgE-mediated immunologic reactions. Reported rates of anaphylaxis were <0.1 percent of administrations for each of several preparations [33,63,64]. Hetastarch is used in major surgeries expected to cause significant fluid shifts (eg, trauma). Dextran is less commonly used as a volume expander, but its antiplatelet effects make it useful as an adjunct to some vascular procedures.
Human albumin has also been implicated in rare perioperative anaphylactic reactions, although the mechanisms have not been explored [65,66]. In addition, gelatin in the plasma expanders polygeline (eg, Haemaccel) and succinylated gelatins (eg, Gelofusine) has caused IgE-mediated anaphylactic reactions [25,67-70]. Gelatin-containing plasma expanders are not in use in the United States, although they are used in other countries. (See "Intraoperative fluid management", section on 'Gelatins'.)
Role of alpha-gal allergy — In the Southeastern United States, as well as areas of Europe, Asia, and Australia, there is growing awareness that patients can develop an allergy to a carbohydrate moiety called galactose-alpha-1,3-galactose (alpha-gal), which is abundantly expressed on cells and tissues of all mammalian species except primate mammals (ie, humans, chimpanzees, and old world monkeys). Patients sensitized to alpha-gal may report delayed allergic reactions to ingestion of a wide range of mammalian meats, most commonly beef, pork, and lamb. In the perioperative setting, they can also react to animal-derived products, including gelatin-based colloids [71] and bovine or porcine heart valves [72]. Some reactions to heparin and to hemostatic agents derived from gelatin (eg, Gelfoam) may also prove to be related to alpha-gal allergy [73], although most are probably not. Reactions range in severity from transient urticaria to anaphylaxis. Understanding of the role of alpha-gal versus other allergens is evolving, and it is not clear how widespread this allergy is. In geographical areas where sensitization to alpha-gal is known to be present, clinicians should be aware of these potential interactions and ask patients about allergic reactions to meat ingestion during preoperative planning. A positive history would not necessarily preclude the use of animal-derived products, but the surgical team should have increased vigilance so that reactions are detected promptly. Case reports have described successful use of premedications as well [74]. Alpha-gal allergy is discussed in more detail separately. (See "Allergy to meats", section on 'Alpha-gal'.)
Hypnotic induction agents — Hypnotic induction agents account for approximately 2 percent of perioperative anaphylaxis cases [3]. There are two types of induction agents: barbiturates (eg, thiopental, methohexital) and nonbarbiturates (eg, propofol, etomidate, ketamine, benzodiazepines). (See "General anesthesia: Intravenous induction agents".)
●Barbiturates – Intravenous barbiturates were previously widely used in anesthesia, and as a class, they account for most reactions to induction agents. Women are affected three times more often than men [22,34]. Most reactions caused by barbiturate induction agents are IgE-mediated, although direct mast cell activation has also been described (table 2) [14,33,75,76]. There is some immunologic cross-reactivity among the barbiturates [75]. Thiopental and thiamylal are no longer available in the United States but are still used in other countries.
●Nonbarbiturates – Anaphylaxis to nonbarbiturate induction agents is very rare. Propofol is a nonbarbiturate induction agent that was initially solubilized in Cremophor (polyethoxylated castor oil), a vehicle that causes non-IgE-mediated anaphylactic reactions [77]. Subsequently, the vehicle for propofol was changed to a soybean oil emulsion with egg phosphatide and glycerol [77-79]. Allergic reactions to these newer preparations appear to be even rarer. Although allergies to egg or soybean are listed in the product information as contraindications to use [80], the vast majority of egg- and soy-allergic subjects tolerate propofol [81,82].
Benzodiazepines are also nonbarbiturate induction agents. Hypotension following intravenous administration is a known adverse effect of these agents, although anaphylactic reactions are very rare [83]. Benzodiazepines may be capable of activating mast cells in vitro [14]. Skin testing with benzodiazepines has been reported [84], although the significance of a positive wheal-and-flare skin reaction is unknown. Cross-reactivity between propofol and benzodiazepines has not been reported and is unlikely.
Opioids — Opioids used in anesthesia/analgesia are a common cause of flushing and urticaria following intravenous administration, although opioids rarely cause life-threatening reactions. Typically, opioids cause limited cutaneous symptoms that are non-IgE-mediated. Morphine or meperidine can cause degranulation of dermal mast cells and release of histamine and other mediators, leading to flushing and urticaria, although rarely angioedema, bronchospasm, or hypotension [17].
Specific IgE to morphine or fentanyl has been implicated in case reports, although skin testing with opioids requires specific dilutions, because direct mast cell activation, particularly by morphine and codeine, can result in false-positive results [85,86]. Fentanyl and sufentanil are less likely to directly activate mast cells but may cause mast cell degranulation through specific, potent mu receptors. However, testing with fentanyl and sufentanil may cause false-positive results due to direct vasodilation [87]. Skin testing to opioids is reviewed separately. (See "Perioperative anaphylaxis: Evaluation and prevention of recurrent reactions", section on 'Opioids'.)
Latex — Natural rubber latex historically has accounted for approximately 20 percent of perioperative anaphylaxis cases and is still a common cause in countries in which latex gloves are routinely used [2,3,22]. However, exposure to latex has been dramatically reduced in most surgical suites in the United States and other countries. The 2018 United Kingdom national registry reported no cases of latex allergy among 266 patients with grade 3 or 4 perioperative anaphylaxis, possibly due to awareness of medical personnel and patients regarding this possibility, as well as increasing use of latex-free materials in hospital settings [25,88].
Anaphylaxis to latex is an IgE-mediated process resulting from the formation of specific IgE against proteins from natural rubber latex. There are a variety of potential sources of latex in surgical and procedural settings (table 3). The most common sources of significant latex exposure in the perioperative setting are flexible items from which latex allergen is easily eluted and that have prolonged contact with skin or mucosal surfaces, such as:
●Gloves (sterile and exam)
●Drains (Penrose and others)
●Catheters (indwelling, straight, and condom)
Hard rubber items, such as straps, tubing, and blood pressure cuffs, elute little or no latex protein and do not contact patient tissues to the same extent as surgical gloves, catheters, and drains. Items that are usually latex-free include bags used in manual ventilation, leg straps for catheter bags, bandages and adhesive pads, tape, electrode pads, endotracheal tubes, infusion sets and ports, and suction catheters.
Reactions to latex tend to occur later in surgical procedures (eg, 30 minutes or more after the start of the intervention). Symptoms may develop after visceral surfaces have been handled or manipulated by surgeons wearing latex gloves.
Latex allergy is more likely in subjects with repeated exposure to latex gloves or catheters from prior surgeries or from occupational use, especially children with spina bifida and health care workers [89]. Sensitization to latex can occur as a result of contact with nonmedical sources of latex as well (eg, condoms, balloons, household gloves), and reactions are not limited to patients in high-risk groups. Latex allergy is reviewed in detail separately. (See "Latex allergy: Epidemiology, clinical manifestations, and diagnosis" and "Latex allergy: Management".)
Other agents — A variety of other medications and agents have been implicated in anaphylaxis or reactions resembling anaphylaxis [13]. Collectively, these other agents account for less than 5 percent of all episodes of perioperative anaphylaxis [3]. Some of these agents are not administered by the anesthesiologist, but awareness of their potential to cause anaphylaxis is necessary for prompt recognition and treatment [88]. Skin testing protocols for some of these agents are discussed separately (see "Perioperative anaphylaxis: Evaluation and prevention of recurrent reactions", section on 'Specific agents'):
●Radiocontrast agents (see "Diagnosis and treatment of an acute reaction to a radiologic contrast agent")
●Blood transfusion (see "Immunologic transfusion reactions")
●Metabisulfites and bisulfites used as preservatives in medications [90-94]
●Nonsteroidal anti-inflammatory drugs (see "NSAIDs (including aspirin): Allergic and pseudoallergic reactions")
●Povidone in the topical antiseptic povidone-iodine [95,96]
●Bacitracin used in irrigation solutions [97-101]
●The sterilization agents ethylene oxide and ortho-phthalaldehyde (Cidex OPA [brand name]) [102-107]
●Streptokinase or urokinase [108,109]
●Isosulfan blue dye (used to detect positive sentinel lymph nodes and malignant melanoma) and other vital dyes [25,110-113]
●Chymopapain (used in herniated disc surgery) and papain [114-117]
●Insulin [118,119] (see "Hypersensitivity reactions to insulins")
●Local anesthetics [120,121] (see "Allergic reactions to local anesthetics")
●Heparin and other anticoagulants: These reactions have been attributed to several mechanisms, including an IgG immune response to platelet factor 4 [122], as well as IgE-mediated reactions to unidentified antigens [123] (see 'Role of alpha-gal allergy' above and "Clinical presentation and diagnosis of heparin-induced thrombocytopenia", section on 'Anaphylaxis')
●Gelatin-containing surgical sponges and topical bovine thrombin hemostatic agents [124,125]
●Protamine, used to reverse heparinization [126-128] (see "Hypersensitivity reactions to insulins")
●Aprotinin, administered either intravenously or as a component of biologic sealants [3,15,129,130]
●Hyaluronidase, used to enhance the diffusion of other drugs and agents [131-135]
RISK FACTORS — Risk factors for perioperative anaphylaxis include female sex (for certain medications), mast cell disorders, multiple past surgeries or procedures (especially for latex and ethylene oxide), and history of anaphylaxis, allergic drug reactions, or other allergic conditions (such as asthma, eczema, or hay fever). In addition, a 2018 registry identified obesity, increased American Society of Anesthesiologists Physical Health score, and beta-blocker and/or angiotensin-converting enzyme inhibitor therapy as risk factors for death or cardiac arrest among 286 cases of more severe perioperative anaphylaxis [25]. However, even in patients at increased risk, perioperative anaphylaxis is an uncommon event.
●Patients with asthma 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 [3,136,137]. In a series of 106 patients, a history of asthma was not associated with an increased risk of intraoperative anaphylaxis or of developing bronchospasm during intraoperative anaphylaxis [138]. The only factor that was associated with increased risk of bronchospasm was exposure to neuromuscular-blocking agents (NMBAs). Bronchospasm occurred with other symptoms of anaphylaxis in 30 percent of cases and as an isolated manifestation of a reaction in 3 percent.
●Women are at higher risk than men for reactions to NMBAs and hypnotic induction agents, although reactions are equal for males and females before adolescence.
●Previous medication reactions nonspecifically increase the possibility of future adverse medication reactions, and multiple previous drug reactions pose a proportionately greater risk.
●Patients with multiple past surgeries or other procedures may be at increased risk for latex allergy and reactions to NMBAs. (See "Latex allergy: Epidemiology, clinical manifestations, and diagnosis", section on 'Diagnosis'.)
●Patients with mast cell disorders, including 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) [139]. Thus, these patients require specific precautionary management prior to procedures or surgery. (See "Advanced systemic mastocytosis: Management and prognosis" and "Mast cell disorders: An overview", section on 'Mast cell physiology'.)
CLINICAL MANIFESTATIONS AND DIAGNOSIS — The diagnosis of perioperative anaphylaxis is clinical and based upon the presence of characteristic signs and symptoms that begin suddenly and progress rapidly in most cases. There is no definitive test to prove or disprove anaphylaxis.
Characteristic signs and symptoms — There are important differences in the presentation of anaphylaxis in an intubated and sedated patient compared with an ambulatory patient (table 4) [140]. In the perioperative setting, early or mild symptoms, such as itching or shortness of breath, may go unnoticed if the patient cannot communicate. Skin symptoms may be present but may not be noticed if the skin is draped or covered. Therefore, anaphylaxis is more likely to present as sudden changes in cardiovascular or respiratory parameters [25,113]. Cardiovascular collapse, which can present with signs ranging from hypotension to cardiac arrest, is the first detected manifestation in up to 50 percent of cases [6,25].
●Hypotension is common during anesthetic induction (especially with propofol). Recognizing hypotension that is part of anaphylaxis can also be complicated by the effects of positive pressure ventilation, surgical manipulation, and sympathectomy associated with spinal/epidural anesthesia. Additional causes of hypotension are discussed below. (See 'Other causes of hypotension/shock' below.)
●Bronchospasm may present as a sudden increase in the ventilatory pressure required to inflate the lungs, an upsloping pattern in the end-tidal carbon dioxide waveform or a decrease in arterial oxygen saturation.
●Rapidly developing laryngeal edema may present as difficulty with intubation or as postextubation stridor.
●Tachycardia is a classic cardiovascular sign of anaphylaxis, although bradycardia occasionally develops later in the reaction if the patient becomes hypoxemic or develops heart block [141].
As a result of these factors, anaphylaxis may be recognized only when dramatic respiratory and hemodynamic changes develop.
Timing — Anaphylaxis due to an IgE-mediated reaction usually develops within a few minutes to approximately 20 minutes following intravenous administration of the causal agent. Symptoms may manifest later if the trigger was administered orally, intramuscularly, or through contact with skin or tissues (latex). Timing of the reaction with respect to the onset of anesthesia may provide additional clues to the underlying cause:
●Allergic reactions occurring during the first 30 minutes of anesthesia are more likely due to antibiotics, neuromuscular-blocking agents, or hypnotic induction agents, because these agents are given at the start of the procedure.
●Anaphylaxis presenting after the first 30 minutes of anesthetic induction are more likely due to agents that are used during or at the conclusion of a surgical procedure, such as latex, blood products, colloid volume expanders, vital dyes, or protamine.
●Sugammadex, a polysaccharide compound, is increasingly reported as a cause of anaphylaxis (approximately 1:33,000) at the conclusion of anesthesia, as this agent is used to reverse muscle paralysis. Sugammadex was US Food and Drug Administration (FDA)-approved in December 2015 and likely there will be increased use in the United States [53,54].
Reactions may also occur after sudden shifts in blood or other fluids, such as removal of a tourniquet, unclamping of blood vessels, or after uterine manipulation followed by administration of oxytocin [2,142,143]. If the trigger was administered or applied by the surgeon (eg, antibiotics in irrigation solutions, topical hemostatic agents, injections of a vital dye for lymph node identification), the anesthesiologist may not immediately make the connection between the exposure and the reaction, so a careful review of the events preceding the reaction with the entire team is critical. (See "Overview of topical hemostatic agents and tissue adhesives".)
Severity — Perioperative anaphylaxis tends to be severe and has a higher mortality rate than anaphylaxis occurring in other settings. Estimates of mortality due to perioperative anaphylaxis range from 1.4 to 6 percent, with another 2 percent of patients surviving with anoxic cerebral injury [12,58,137,144]. In contrast, fatal anaphylaxis from all causes has been estimated to be 0.7 to 2 percent of cases. The heightened severity of perioperative anaphylaxis may be attributable to the intravenous route of drug administration and/or the factors that impair early recognition of reactions. Another possibility is that individuals receiving anesthesia may be more vulnerable to physiologic perturbations, especially following spinal/epidural anesthesia, which may cause a sympathectomy. The concomitant stresses of surgery or illness may also contribute.
IgE-mediated anaphylaxis is generally more severe than non-IgE-mediated anaphylaxis [3], although both types can be fatal. A review of fatal anaphylaxis from all causes is presented separately. (See "Fatal anaphylaxis".)
MANAGEMENT
Initial management — The treatment of anaphylaxis during anesthesia is based on prompt hemodynamic resuscitation that includes epinephrine, fluids, and other strategies (table 5). The perioperative/intensive care unit setting is one of the few places that intravenous bolus epinephrine is used regularly in initial management, outside of advanced cardiac life support algorithms. For acute shock and cardiopulmonary dysfunction, it is essential to use intravenous treatment agents, carefully titrated to specific effects. In most other settings, clinicians should use intramuscular epinephrine for anaphylaxis.
A detailed discussion of anaphylaxis management in other settings is found separately. (See "Anaphylaxis: Emergency treatment".)
Subsequent allergy evaluation should take place after the patient has recovered fully. This evaluation is reviewed separately. (See 'Referral for allergy evaluation' below and "Perioperative anaphylaxis: Evaluation and prevention of recurrent reactions".)
Laboratory tests at the time of the reaction — Blood collected at the time of the reaction (or shortly after) may reveal elevations in tryptase, a mediator released nearly exclusively by mast cells and basophils. The release of tryptase can help distinguish anaphylaxis from other perioperative events, such as cardiogenic shock [145,146]. However, not all episodes of anaphylaxis result in elevations in tryptase, so a normal tryptase does not exclude anaphylaxis. Tryptase was elevated in 68 percent of IgE-mediated reactions and 4 percent of non-IgE-mediated reactions in the largest French study [3]. Elevations in serum tryptase are most often detected in cases of anaphylaxis that involve hypotension.
Serum tryptase has a half-life of approximately two hours. Blood for serum tryptase should be collected as soon as possible after the onset of symptoms [147]. Thirty minutes to three hours after the onset of symptoms is optimal, although increases may be detectable longer following massive mast cell activation. Blood for serum tryptase should be collected in a red-top tube, and a minimum of 1 mL is recommended.
A serum tryptase >11.4 ng/mL is considered elevated. However, an increase in tryptase can occur with mast cell activation and not exceed the normal range if the baseline level for that individual is low. An increase in serum total tryptase of 20 percent + 2 ng/mL is accepted as evidence of mast cell activation. The equation 1.2 x baseline tryptase + 2 ng/mL is used to calculate the level indicative of mast cell activation [148]. For example, if a patient's baseline tryptase is 2 ng/mL, then a level of 7 ng/mL drawn shortly after a perioperative reaction is consistent with anaphylaxis. In most cases, the patient's baseline serum tryptase is not known, but it can be obtained by repeating the serum tryptase several days after the reaction, as tryptase is rapidly cleared from the circulation. The interpretation of laboratory tests in patients with anaphylaxis is discussed in more detail elsewhere. (See "Laboratory tests to support the clinical diagnosis of anaphylaxis".)
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 and not the heart. (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 of limited clinical value. (See "Laboratory tests to support the clinical diagnosis of anaphylaxis".)
Decisions regarding proceeding with surgery — The decision to proceed with surgery following anaphylaxis should be individualized depending on the severity of the reaction, cardiopulmonary stability, and the urgency of the procedural intervention. Ultimately, the clinicians involved must use clinical judgement to determine the most sensible course of action. In one retrospective analysis, proceeding with surgery was safe after grade 1 or 2 anaphylactic reactions (limited to cutaneous signs and/or vital sign changes that are not life-threatening). After grade 3 reactions (profound hypotension or severe bronchospasm), the risk of adverse events attributable to the reaction was higher but did not differ in cases where surgery was continued or abandoned [149]. Surgical procedures were frequently abandoned after grade 4 reactions (associated with cardiac arrest and/or inability to ventilate) in this study, although there was no evidence of further harm as a result of proceeding with emergency or partially completed major surgery. In the 2018 United Kingdom prospective registry, the surgical procedure was not started or abandoned in more than one-half of the cases with a grade 3 or higher anaphylactic reaction, including 10 percent where surgery was urgent [58].
REFERRAL FOR ALLERGY EVALUATION — Patients with suspected perioperative anaphylaxis should be referred to an allergy specialist. The evaluation is best performed no sooner than one month after the reaction (because mast cells in the skin may be relatively unresponsive immediately after an episode of widespread hives or flushing) but within the next year (because testing is less likely to be informative if many years have passed since the reaction).
To maximize the likelihood of identifying the culprit allergen, the referring anesthesiologist and/or surgeon should provide the following information to the allergist:
●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, dyes, or other agents or 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.
●Whether surgical instruments were used in the procedure (because disinfectant chemicals can be allergens).
●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 of skin testing for most drugs, other than penicillin, is not well-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 [150]. The few cases of repeat anaphylaxis were attributed to either limitations in the historical information provided to the allergy consultant or to 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.
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 [30,151,152]. Tryptase levels should be normal in all of these other disorders:
Other causes of respiratory or airway symptoms
●Acute asthmatic reaction (see "Anesthesia for adult patients with asthma", section on 'Intraoperative bronchospasm')
●Aspiration
●Endotracheal tube malposition
●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 outside of the operating room", section on 'Trismus')
●Postextubation stridor (see "Respiratory problems in the post-anesthesia care unit (PACU)", section on 'Upper airway obstruction')
●Pulmonary edema
●Pulmonary embolus (see "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism")
●Tension pneumothorax
●Transfusion-related acute lung injury (TRALI) (see "Transfusion-related acute lung injury (TRALI)", section on 'Clinical presentation')
(See "Assessment of respiratory distress in the mechanically ventilated patient".)
Other causes of hypotension/shock
●Arrhythmias
●Cardiac tamponade (see "Cardiac tamponade", section on 'Acute cardiac tamponade')
●Cardiogenic shock
●Hemorrhage
●Hyperkalemia
●Overdose of vasoactive drugs
●Partial sympathectomy from spinal/epidural anesthesia
●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: Acute treatment of angioedema attacks")
●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 usually be excluded by the negative results of an ice cube challenge, except for familial cold urticaria associated with cryopyrin dysfunction [153]. (See "Cold urticaria".)
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: Anaphylaxis".)
SUMMARY AND RECOMMENDATIONS
●Anaphylaxis is a potentially lethal reaction usually resulting from the sudden, clinically significant release of mast cell- and/or basophil-derived mediators into the circulation. Both immunoglobulin E (IgE) and non-IgE-mediated immune mechanisms have been implicated, and some agents may cause reactions by more than one mechanism (table 1 and table 2). (See 'Mechanisms of anaphylaxis' above.)
●The more common identifiable causes of perioperative anaphylaxis are antibiotics, neuromuscular-blocking agents, chlorhexidine, and sugammadex. However, there is a much longer list of agents that are implicated less commonly. (See 'Etiologies' above.)
●Risk factors for perioperative anaphylaxis include female sex (for certain medications), other allergic conditions (eg, asthma, eczema, or hay fever), multiple past surgeries or procedures (especially for latex), and mast cell disorders. (See 'Risk factors' above.)
●Perioperative anaphylaxis may exhibit cutaneous, respiratory, and cardiovascular signs and symptoms, as well as variable involvement of other organ systems, although these signs may be more difficult to recognize in sedated or anesthetized patients (table 4). The diagnosis is clinical. One-half of cases are initially detected as sudden cardiovascular collapse. Bronchospasm may present as an increase in the ventilatory pressure required to inflate the lungs or as a decrease in arterial oxygen saturation. (See 'Clinical manifestations and diagnosis' above.)
●Perioperative anaphylaxis tends to be severe and has a higher mortality rate than anaphylaxis occurring in other settings. This is at least partly attributable to factors that impair early recognition of anaphylaxis, such as the inability of the patient to report initial symptoms and coverage of the skin with surgical drapes. The intravenous administration of triggering drugs and concomitant stresses of surgery or illness may also contribute. (See 'Severity' above.)
●The treatment of anaphylaxis during anesthesia is based on cardiopulmonary resuscitation that includes prompt administration of epinephrine and fluid resuscitation (table 5). Intravenous epinephrine is commonly used in the operating room while the patient is monitored, and intravenous access is readily available. (See 'Initial management' above.)
●An increase from baseline or elevated serum total tryptase, ideally obtained within three hours of a suspected reaction, is highly suggestive of anaphylaxis, although normal levels do not exclude the diagnosis. Total tryptase should be measured again after recovery to exclude the possibility that tryptase is chronically elevated due to a mast cell disorder and to obtain a baseline tryptase value for comparison with results during the event. An increase of 1.2 x baseline tryptase + 2 ng/mL during the suspected anaphylaxis is consistent with a mast cell-mediated event. Thus, a normal acute tryptase value may still suggest mast cell-mediator release if the baseline level is low. (See 'Laboratory tests at the time of the reaction' above and 'Differential diagnosis' above.)
●Patients who experience perioperative anaphylaxis should be referred to an allergy specialist. Clinical history and record review are used to determine all of the agents to which the patient was exposed leading up to the reaction. The allergist performs skin testing if feasible and appropriate to identify the likely culprit drug and/or to recommend alternative agents. This approach allows most patients to undergo future anesthesia safely. (See 'Referral for allergy evaluation' above.)
1 : The incidence and clinical features of anaphylactic reactions during anesthesia in Australia.
2 : [Epidemiology of anesthetic anaphylactoid reactions. Fourth multicenter survey (July 1994-December 1996)].
3 : Anaphylaxis during anesthesia in France: an 8-year national survey.
4 : Reducing the risk of anaphylaxis during anesthesia: 2011 updated guidelines for clinical practice.
5 : Epidemiology of perioperative anaphylaxis.
6 : Symposium on the definition and management of anaphylaxis: summary report.
7 : 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.
8 : Mechanisms of anaphylaxis beyond classically mediated antigen- and IgE-induced events.
9 : Serum tryptase determination in patients with acute allergic reactions.
10 : Molecular mechanisms of anaphylaxis: lessons from studies with murine models.
11 : Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003.
12 : Reducing the risk of anaphylaxis during anaesthesia: guidelines for clinical practice.
13 : Peri-anesthetic anaphylaxis.
14 : Role of mast cells, basophils and their mediators in adverse reactions to general anesthetics and radiocontrast media.
15 : Anaphylaxis during cardiac surgery: implications for clinicians.
16 : Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions.
17 : Mechanisms of nonimmunological histamine and tryptase release from human cutaneous mast cells.
18 : General anaesthesia-induced anaphylaxis: impact of allergy testing on subsequent anaesthesia.
19 : Hypersensitivity reactions during anesthesia. Results from the ninth French survey (2005-2007).
20 : Hypersensitivity reactions in the anesthesia setting/allergic reactions to anesthetics.
21 : Anaesthetic hypersensitivity reactions in France between 2011 and 2012: the 10th GERAP epidemiologic survey.
22 : Anaphylactic and anaphylactoid reactions occurring during anesthesia in France in 1999-2000.
23 : Danish Anaesthesia Allergy Centre - preliminary results.
24 : Anaphylaxis during general anaesthesia: experience from a drug allergy centre in the UK.
25 : Anaesthesia, surgery, and life-threatening allergic reactions: epidemiology and clinical features of perioperative anaphylaxis in the 6th National Audit Project (NAP6).
26 : Intraoperative Anaphylaxis to Chlorhexidine During LVAD and Transplant Surgery.
27 : Anaphylaxis during anesthesia in Norway: a 6-year single-center follow-up study.
28 : Allergic reactions during anesthesia at a large United States referral center.
29 : Antibiotics Are the Most Commonly Identified Cause of Perioperative Hypersensitivity Reactions.
30 : Perioperative anaphylaxis.
31 : Immunoglobulin E-mediated hypersensitivity reaction after intraperitoneal administration of vancomycin.
32 : Immune-mediated reactions to vancomycin: A systematic case review and analysis.
33 : Allergy during anaesthesia.
34 : Mechanisms in IgE-dependent anaphylaxis to anesthetic drugs.
35 : Different patterns of mast cell activation by muscle relaxants in human skin.
36 : Onset time, endotracheal intubating conditions, and plasma histamine after cisatracurium and vecuronium administration.
37 : Substituted ammonium ions as allergenic determinants in drug allergy.
38 : Pholcodine exposure raises serum IgE in patients with previous anaphylaxis to neuromuscular blocking agents.
39 : Prevalence of IgE antibodies to morphine. Relation to the high and low incidences of NMBA anaphylaxis in Norway and Sweden, respectively.
40 : National pholcodine consumption and prevalence of IgE-sensitization: a multicentre study.
41 : A mechanism for rapacuronium-induced bronchospasm: M2 muscarinic receptor antagonism.
42 : An unexpected cause of an acute hypersensitivity reaction during recovery from anaesthesia.
43 : Chlorhexidine anaphylaxis: a case report and review of the literature.
44 : Anaphylaxis to the chlorhexidine component of Instillagel: a case series.
45 : IgE-mediated allergy to chlorhexidine.
46 : Multi-centre retrospective analysis of anaphylaxis during general anaesthesia in the United Kingdom: aetiology and diagnostic performance of acute serum tryptase.
47 : Life-threatening anaphylactic shock due to chlorhexidine on the central venous catheter: a case series.
48 : Chlorhexidine: a new latex?
49 : Chlorhexidine Anaphylaxis Masquerading as Septic Shock.
50 : Chlorhexidine-induced anaphylaxis in surgical patients: a review of the literature.
51 : Incidence of Anaphylaxis Associated With Sugammadex.
52 : Incidence of hypersensitivity and anaphylaxis with sugammadex.
53 : Sugammadex: An emerging trigger of intraoperative anaphylaxis.
54 : Anaphylaxis to sugammadex diagnosed by skin prick testing using both sugammadex and a sugammadex-rocuronium mixture.
55 : Allergy to low dose sugammadex.
56 : Drug-specific cyclodextrins with emphasis on sugammadex, the neuromuscular blocker rocuronium and perioperative anaphylaxis: implications for drug allergy.
57 : Hypersensitivity associated with sugammadex administration: a systematic review.
58 : Anaesthesia, surgery, and life-threatening allergic reactions: management and outcomes in the 6th National Audit Project (NAP6).
59 : Hypersensitivity incidence after sugammadex administration in healthy subjects: a randomised controlled trial.
60 : Sugammadex hypersensitivity and underlying mechanisms: a randomised study of healthy non-anaesthetised volunteers.
61 : Sugammadex: the sting in the tail?
62 : Intravenous fluid therapy in critically ill adults.
63 : Anaphylactoid reactions to Dextran 40 and 70: reports to the United States Food and Drug Administration, 1969 to 2004.
64 : Hydroxyethyl starch--can the safety problems be ignored?
65 : Prick tests in the diagnosis of anaphylaxis to general anaesthetics.
66 : Anaphylactoid shock in a patient following 5% human serum albumin infusion during off-pump coronary artery bypass grafting.
67 : Anaphylaxis to intravenous gelatin-based solutions: a case series examining clinical features and severity.
68 : Anaphylaxis to intravenous gelatin-based solutions: a case series examining clinical features and severity.
69 : Anaphylactic reactions to modified fluid gelatins.
70 : Anaphylaxis to Haemaccel and cross reactivity to Gelofusin.
71 : Anaphylaxis to succinylated gelatin in a patient with a meat allergy: galactose-α(1, 3)-galactose (α-gal) as antigenic determinant.
72 : Porcine or bovine valve replacement in 3 patients with IgE antibodies to the mammalian oligosaccharide galactose-alpha-1,3-galactose.
73 : Invited Commentary: Alpha-Gal Allergy: Tip of the Iceberg to a Pivotal Immune Response.
74 : Impact of newly emerging alpha-gal allergies on cardiac surgery: A case series.
75 : Anaphylaxis during induction of general anesthesia: subsequent evaluation and management.
76 : Thiobarbiturate-induced histamine release in human skin mast cells.
77 : Propofol: the challenges of formulation.
78 : Propofol: therapeutic indications and side-effects.
79 : Development of a new generation of propofol.
80 : Possible anaphylaxis after propofol in a child with food allergy.
81 : Potential food allergens in medications.
82 : No evidence for contraindications to the use of propofol in adults allergic to egg, soy or peanut†.
83 : Benzodiazepine Allergy With Anesthesia Administration: A Review of Current Literature.
84 : Adverse reaction to tetrazepam.
85 : Anaphylaxis to intrathecal diamorphine.
86 : Anaphylactic reaction during anaesthesia associated with positive intradermal skin test to fentanyl.
87 : Wheal and flare responses to opioids in humans.
88 : Changing culprits in perioperative anaphylaxis.
89 : Prevalence and risk factors for latex allergy.
90 : Positive skin tests and Prausnitz-Küstner reactions in metabisulfite-sensitive subjects.
91 : Anaphylaxis after administration of amikacin containing sodium metabisulfite in a premature newborn.
92 : Clonal mast cell activation syndrome with anaphylaxis to sulfites.
93 : Anaphylactic cardiovascular collapse during anesthesia: the Kounis acute hypersensitivity syndrome seems to be the most likely cause.
94 : Propofol allergy: assessing for patient risks.
95 : Acute IgE-mediated generalized urticaria-angioedema after topical application of povidone-iodine.
96 : Recurrent anaphylaxis caused by topical povidone-iodine (Betadine).
97 : Bacitracin irrigation: a cause of anaphylaxis in the operating room.
98 : Intraoperative anaphylactic shock after bacitracin irrigation.
99 : Intraoperative anaphylaxis associated with bacitracin irrigation.
100 : Detection of IgE antibodies to bacitracin using a commercially available streptavidin-linked solid phase in a patient with anaphylaxis to triple antibiotic ointment.
101 : Intraoperative anaphylaxis to bacitracin during pacemaker change and laser lead extraction.
102 : Haemodialysis-associated anaphylactic and anaphylactoid reactions.
103 : A comparison of cutaneous testing and ELISA testing for assessing reactivity to ethylene oxide-human serum albumin in hemodialysis patients with anaphylactic reactions.
104 : Three cases of ortho-phthalaldehyde-induced anaphylaxis after laryngoscopy: detection of specific IgE in serum.
105 : Nine episodes of anaphylaxis following cystoscopy caused by Cidex OPA (ortho-phthalaldehyde) high-level disinfectant in 4 patients after cytoscopy.
106 : Anaphylaxis following cystoscopy with equipment sterilized with Cidex OPA (ortho-phthalaldehyde): a review of two cases.
107 : Ortho-phthalaldehyde-induced anaphylaxis after laryngoscopy.
108 : Anaphylactic reactivity to streptokinase.
109 : Hypersensitivity reactions associated with recombinant tissue-type plasminogen activator and urokinase.
110 : Anaphylaxis to patent blue V: a case series and proposed diagnostic protocol.
111 : Anaphylaxis to isosulfan blue and cross-reactivity to patent blue V: case report and review of the nomenclature of vital blue dyes.
112 : Adverse drug reaction, patent blue V dye and anaesthesia.
113 : Anaesthesia-associated hypersensitivity reactions: seven years' data from a British bi-specialty clinic.
114 : Anaphylactic shock associated with chymopapain skin test. A case report and review of the literature.
115 : Anaphylactoid reaction to chymopapain.
116 : Safety of chemonucleolysis. Adverse effects reported in the United States, 1982-1991.
117 : Incidence and risk factors for latent sensitization to chymopapain: predictive skin-prick tests in 700 candidates for chemonucleolysis.
118 : [Insulin allergy: background, diagnosis and treatment].
119 : Insulin allergy.
120 : Approach to patients with suspected hypersensitivity to local anesthetics.
121 : Anaphylactic reactions to local anesthetics.
122 : Concurrence of anaphylaxis and acute heparin-induced thrombocytopenia in a patient with heparin-induced antibodies.
123 : Hypersensitivity reactions to heparins.
124 : Intraoperative anaphylaxis induced by the gelatin component of thrombin-soaked gelfoam in a pediatric patient.
125 : Intraoperative anaphylaxis to gelatin in topical hemostatic agents during anterior spinal fusion: a case report.
126 : Protamine and protamine reactions.
127 : Serious anaphylactic reactions due to protamine sulfate: a systematic literature review.
128 : Three Cases of Anaphylaxis to Protamine: Management of Anticoagulation Reversal.
129 : Anaphylactic reaction after systemic application of aprotinin triggered by aprotinin-containing fibrin sealant.
130 : Aprotinin and anaphylaxis: analysis of 12,403 exposures to aprotinin in cardiac surgery.
131 : Flow-assisted diagnosis of anaphylaxis to hyaluronidase.
132 : Hyaluronidase allergy after peribulbar anesthesia with orbital inflammation.
133 : Angioedema related to the use of hyaluronidase in cataract surgery.
134 : Hyaluronidase allergy: a rare cause of periorbital inflammation.
135 : Allergic reaction to hyaluronidase after retrobulbar anaesthesia: a case series and review.
136 : The epidemiology and clinical features of anaphylactic reactions in anaesthesia.
137 : Anaphylaxis to anaesthetic drugs.
138 : Anaphylactic bronchospasm during general anesthesia is not related to asthma.
139 : Systemic mastocytosis presenting as intraoperative anaphylaxis with atypical features: a report of two cases.
140 : Anaphylaxis during anaesthesia. Results of a two-year survey in France.
141 : Slowing of the heart during anaphylactic shock. A report of five cases.
142 : [Anaphylactic shock after tourniquet removal in orthopedic surgery].
143 : Anaphylaxis complicating graft reperfusion during orthotopic liver transplantation: a case report.
144 : Survival from perioperative anaphylaxis in Western Australia 2000-2009.
145 : Tryptase in diagnosing adverse suspected anaphylactic reaction.
146 : Diagnostic value of histamine and tryptase concentrations in severe anaphylaxis with shock or cardiac arrest during anesthesia.
147 : Comprehensive allergy evaluation is useful in the subsequent care of patients with drug hypersensitivity reactions during anesthesia.
148 : An increase in serum tryptase even below 11.4 ng/mL may indicate a mast cell-mediated hypersensitivity reaction: a prospective study in Hymenoptera venom allergic patients.
149 : Consequences of proceeding with surgery after resuscitation from intra-operative anaphylaxis.
150 : Outcome of repeat anaesthesia after investigation for perioperative anaphylaxis.
151 : Allergy, anaphylaxis and general anesthesia
152 : Perioperative anaphylaxis: diagnosis, evaluation, and management.
153 : Acquired cold urticaria: clinical picture and update on diagnosis and treatment.
