Claudie Mouton-Faivre

Anaphylaxis and anesthesia: controversies and new insights.

PERIOPERATIVE anaphylaxis may be a life-threatening clinical condition and is typically a result of drugs or substances used for anesthesia or surgery. After anaphylaxis, allergologic assessment is essential to identify the offending agent and prevent recurrences, because no preemptive therapeutic strategies exist. This review seeks to (1) identify the clinical diagnostic pathway necessary to distinguish anaphylaxis from confounding clinical diagnoses, (2) discuss the more common allergens that cause anaphylaxis during anesthesia, (3) discuss a rational approach to the identification of the offending allergen through blood and skin testing that allows for the safe future clinical management of patients experiencing perioperative anaphylaxis, and (4) discuss new therapeutic perspectives for the management of patients whose hemodynamic collapse is unresponsive to catecholamines, the initial recommended pharmacologic intervention.

Anaphylaxis to dyes during the perioperative period: Reports of 14 clinical cases

BACKGROUND Vital dyes are widely used for lymphatic mapping and sentinel lymph node biopsy in patients with malignant tumors, and reports of anaphylactic reactions are becoming more frequent. OBJECTIVE Our aims were to describe specific clinical features of hypersensitivity reactions to Patent Blue (Guerbet, Roissy, France), results of the allergy workup, and their consequences for patient management. METHODS We report a series of 14 clinical cases of dye-induced anaphylaxis recorded between 2004 and 2006 in 4 member centers of a network of French allergoanesthesia outpatient clinics. RESULTS Reactions appeared to be relatively severe (6/14 grade III reactions). An average 30 +/- 6-minute delay was observed between dye injection and symptom onset. In 9 (65%) patients reactions were sustained for several hours, requiring prolonged continuous epinephrine infusion and transfer to an intensive care unit. Prick test results were positive in 8 patients. In 5 patients prick test results were negative, whereas intradermal test results were positive. CONCLUSION Anesthesiologists and allergologists must be aware of this specific risk and of the clinical characteristics of these reactions, which are usually delayed and long lasting.

Severe anaphylactic shock with methylene blue instillation.

We report a documented severe immunoglobulin E-mediated hypersensitivity reaction associated with use of 1% methylene blue for detection of tubal permeability occurring during general anesthesia. Clinical symptoms, biological assessment results, and cutaneous test positivity confirmed an anaphylactic reaction to methylene blue. This case report confirms the need for systematic allergological investigation of all drugs and substances administered during the perioperative period in the event of a hypersensitivity reaction occurring during anesthesia. Anesthesiologists should be aware of the possibility of hypersensitivity reactions involving any drug or substance used during surgery.

Immediate reactions following iodinated contrast media injection: A study of 38 cases

OBJECTIVES To investigate the pathomechanisms involved in cases of immediate hypersensitivity reactions occurring after the administration of iodinated contrast media. MATERIALS AND METHODS Patients having presented clinical signs of immediate hypersensitivity suggesting allergy after iodinated contrast medium were investigated. Histamine and tryptase concentrations were measured, and/or skin tests were performed. Patients with positive skin tests to the culprit contrast agent were classified as IgE-mediated allergic hypersensitivity (Group I) and patients with negative skin tests as non-allergic hypersensitivity (Group II). RESULTS 38 patients were included. Most reactions appeared after non-ionic (n = 32). Reactions were more frequently severe following ionic than non-ionic (p = 0.014). Skin testing was not performed in 11 patients. Skin tests with the culprit contrast agent were negative in 26% of the patients (Group II, n = 7) whereas they were found positive with the contrast agent in 73% of the patients (Group I, n = 19). Latex-induced reaction was diagnosed in one patient, and was consequently excluded from the cohort. In Group I, the frequency of cross-reactivity with the other commercialized iodinated contrast media was low (7%). Cardiovascular signs were present in Group I (52.6%, n = 10), and absent in Group II (p = 0.023). Histamine and tryptase concentrations were higher in patients who had cardiovascular signs (p < 0.02). CONCLUSION Immediate reactions with clinical signs suggesting allergy along with positive skin tests with the administered contrast agent confirm immediate allergic hypersensitivity (anaphylaxis) to this agent. Consequently, the culprit contrast agent should be definitely avoided as well as cross-reactive ICM in order to prevent further recurrences.

Anaphylaxis to macrogol 4000 after a parenteral corticoid injection

Pentoxyfylline is a purine derivative. The purines include adenine, guanine, and alkaloids-like caffeine and theophylline. Uric acid is the metabolic end-product of purine metabolism. Pentoxyfylline is used as a vasodilator to relieve symptoms in some cases of intermittent claudication. No immediate hypersensitivity reactions have been described with this product to date. We report the case of a 60-year-old man who had been treated for 2 days with Hemovas (Gupo Ferrer, Division Robert, Barcelona, Spain) 400 mg and consulted for the appearance of red macules that developed into highly pruriginous papules that spread until becoming generalized and led the patient to seek emergency care. One month later, administration of the medication was renewed. Immediately after taking the first tablet of pentoxyfylline 400 mg, the patient presented generalized wheals that remitted within hours of taking antihistamines. The patient gave written consent to undergo hypersensitivity studies. Skin prick and intradermal tests were performed with pentoxyfylline, euphylline, theophylline, allopurinol, azathioprine, and 6-mercaptopurine. Results were positive for intradermal pentoxyfylline, 0.2 mg/ml, in the immediate reading. In 10 controls, the readings were uniformly negative. In response to oral challenge with theophylline 200 mg, the patient reached a cumulative dose of 350 mg with good tolerance. When given therapeutic doses of pentoxyfylline 400 mg, the patient presented within 1 h of the last dose (cumulative dose of 540 mg) generalized, highly pruriginous erythematous papules that remitted with outpatient oral treatment. He was diagnosed of immediate hypersensitivity to pentoxyfylline. In the literature we found reports of the pentoxyfylline use as a modulator of immune activity through the production of cytokines with anti-inflammatory effects. Among the xanthine derivatives, there are studies of theophylline, which also has immunomodulator activity (1–3). We found no published reports of immediate hypersensitivity reactions to pentoxyfylline, and few reports of reactions to methylxanthines, including caffeine and cola products (4, 5). The responsible mechanism appears to be immunoglobulin E (IgE)-mediated hypersensitivity in view of the results of allergy tests. In addition, as has been reported by other authors, the patient showed tolerance to oral theophylline exposure, thus excluding pharmacologic cross-reactions because of molecular similarity to pentoxyfylline (Fig. 1). Consequently, we report what we believe is the first case in the literature of acute urticaria triggered by pentoxyfylline and confirmed by skin tests and an oral challenge.

What investigation after an anaphylactic reaction during anaesthesia

Purpose of review Anaphylactic reactions occurring during anaesthesia may be life threatening. Lethal issues may be involved in up to 3–10% of the cases. The allergological assessment (including biochemical tests and skin tests) is the key to the management of these reactions. The scope of this review is to focus on the allergological assessment required to prove the immune mechanism, to identify the culprit drug or substance and the cross-reactive molecules, especially for neuromuscular blocking agents, allowing preventive measures for future anaesthetic procedures. Recent findings To describe the allergological assessment (including biochemical tests and skin tests performed according to the current guidelines) in order to prove the immune mechanism as the responsibility of the culprit allergen. The most frequent and less frequent drugs involved are described. The different biological tools available are detailed. To ensure an accurate diagnosis, the interpretation of the allergological assessment should be linked to the description of the clinical events as their time onset following the injection/administration of the suspected drug(s)/substance. Summary To describe the different tools (biochemical tests and skin tests) available in order to prove the diagnosis of an anaphylactic reaction occurring during anaesthesia.

Case Scenario: Bronchospasm during Anesthetic Induction

This article has been selected for the ANESTHESIOLOGY CME Program. Learning objectives and disclosure and ordering information can be found in the CME section at the front of this issue.

Apical ballooning syndrome following perioperative anaphylaxis is likely related to high doses of epinephrine

Apical ballooning syndrome, a reversible left ventricle dysfunction, has been reported following anaphylaxis and, during this clinical circumstance, is seemingly linked to the use of either low or high doses of epinephrine. We report a severe succinylcholine-induced IgE-mediated anaphylaxis in a 65-year-old woman, in whom the diagnosis of apical ballooning syndrome following anaphylaxis was established. As a thorough description of the clinical features and resuscitative measures could be obtained, we discuss the reasons for apical ballooning syndrome occurrence and highlight the fact that optimal care management of anaphylaxis should include a progressive titration of epinephrine.

Possible Link Between Apical Ballooning Syndrome During Anaphylaxis and Inappropriate Administration of Epinephrine

To the Editor: Manivannan et al1 published a useful case of apical ballooning syndrome (ABS) after intravenous administration of epinephrine for anaphylaxis. The authors rightly underscored that high doses of intravenous epinephrine may induce ABS. However, specific concerns are warranted regarding some key points. Specifically, ABS occurring after anaphylaxis seems to be related to inappropriate use of epinephrine, including intravenous and intramuscular injections as well as high or low doses. Five clinical cases have been reported for ABS after epinephrine administration for anaphylaxis (Table).2-6 Han and Yeon2 reported the first case, in which 0.2 mg of epinephrine was intravenously injected during moderate anaphylaxis. The authors considered that the midventricular hypokinesis was related to a cardiac manifestation of anaphylaxis. Cabaton et al3 and Suk et al5 reported ABS after perioperative anaphylaxis. Cabaton et al3 showed that epinephrine, even when injected at low intravenous doses, may have been involved in the occurrence of ABS. In this case, the 2 last boluses of epinephrine (0.1 mg × 2) were injected after generalized cutaneous signs appeared (indicating hemodynamic restoration) and were immediately followed by ventricular fibrillation. Suk et al5 reported ABS after a high dose (1 mg) of intravenous epinephrine associated with a norepinephrine infusion. The authors suggested that excessive catecholamine surges in response to anaphylaxis and/or to the administration of exogenous catecholamines may have played a role in the ABS occurrence. In the case published by Manivannan et al,1 2 intravenous doses of 0.5 mg of epinephrine were injected in the absence of cardiovascular disturbances. Hypotension occurring after the first bolus of epinephrine was related to an adverse cardiac response to epinephrine. TABLE. Clinical Cases of ABS After Epinephrine Injection During Anaphylaxisa,b Zubrinich et al4 and Litvinov et al6 reported ABS after intramuscular injection of epinephrine. The former concluded that, given the mild clinical presentation, epinephrine (0.3 mg) should not have been used.4 The latter confirmed a direct causal role for suprapharmacologic doses of exogenous epinephrine (5 mg) in the pathophysiology of ABS.6 The dangers of epinephrine administration outside the context of severe anaphylaxis have been highlighted by the reports of serious outcomes. Recently, pharmacologic and suprapharmacologic doses of epinephrine have been reported to induce one of the 3 ABS variants.6 The catechol O-methyltransferase genotype and intense psychological stress may also influence predisposition to ABS.1,6 Finally, all the reported patients1-6 fulfilled Mayo Clinic criteria for ABS.1 Thus, as suggested during perioperative anaphylaxis, treatment may be initiated according to a 4-step clinical grading scale.7 Whereas grade 1 involves cutaneous-mucous signs in which epinephrine should never be injected, grade 2 corresponds to mild cutaneous-mucous features that may be associated with cardiovascular and/or respiratory signs for which titrated intravenous boluses (0.01-0.02 mg) of epinephrine may sometimes be necessary. The hallmark of grade 3 is cardiovascular collapse that may be associated with cutaneous-mucous signs and/or bronchospasm; titrated intravenous bolus administration of epinephrine (0.1-0.2 mg) is required and should be renewed if necessary. Finally, grade 4 is cardiac arrest that requires high doses of epinephrine, as warranted during cardiopulmonary resuscitation. The important issue is not the route of epinephrine administration, but its appropriate use during anaphylaxis. Consequently, these cases emphasize the need for careful patient selection and titration of epinephrine when the clinical situation dictates its use.

Immediate and Late Adverse Reactions to Iodinated Contrast Media: A Pharmacological Point of View

Iodinated contrast media (CM) are widely used in radiological procedures, and carry a risk of adverse reactions with possible sequelae or death. Various and numerous reactions have been reported, most of which are transient ones and do not threaten the patients life. Immediate adverse reactions include adverse effects directly related to the osmotic load or to the CM chemotoxicity, and immediate hypersensitivity reactions. The exact incidence of the different types of reactions is difficult to establish because not all cases are reported and because a unique severity scale is lacking. All the underlying mechanisms have not been evidenced yet, as patients are rarely properly investigated. Allergic immediate hypersensitivity probably provokes the most severe reactions, whereas non-allergic hypersensitivity determines moderate reactions. Diagnostic tools are available and consist in tryptase and histamine measurements and in skin testing. Late reactions include skin or systemic reactions due to T-lymphocytes-mediated delayed hypersensitivity, nephropathy and dysthyroidism. Delayed allergic hypersentivity can be diagnosed by skin testing with delayed reading. Allergic hypersensitivity, immediate or delayed, means immune mechanisms and is a contraindication of further administration of the culprit CM.