Anaphylaxis

Anesthesiologists use a myriad of drugs during the provision of an anesthetic. Many of these drugs have side effects that are dose related, and some lead to severe immune-mediated adverse reactions. Anaphylaxis is the most severe immune-mediated reaction; it generally occurs on reexposure to a specific antigen and requires the release of proinflammatory mediators. Anaphylactoid reactions occur through a direct non-immunoglobulin E-mediated release of mediators from mast cells or from complement activation. Muscle relaxants and latex account for most cases of anaphylaxis during the perioperative period. Symptoms may include all organ systems and present with bronchospasm and cardiovascular collapse in the most severe cases. Management of anaphylaxis includes discontinuation of the presumptive drug (or latex) and anesthetic, aggressive pulmonary and cardiovascular support, and epinephrine. Although a serum tryptase confirms the diagnosis of an anaphylactic reaction, the offending drug can be identified by skin-prick, intradermal testing, or serologic testing. Prevention of recurrences is critical to avoid mortality and morbidity.

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Anaphylaxis during the perioperative period.

Risk assessment of individuals with anaphylaxis is currently hampered by lack of (1) an optimal and readily available laboratory test to confirm the clinical diagnosis of an anaphylaxis episode and (2) an optimal method of distinguishing allergen-sensitized individuals who are clinically tolerant from those at risk for anaphylaxis episodes after exposure to the relevant allergen. Our objectives were to review the effector mechanisms involved in the pathophysiology of anaphylaxis; to explore the possibility of developing an optimal laboratory test to confirm the diagnosis of an anaphylaxis episode, and the possibility of improving methods to distinguish allergen sensitization from clinical reactivity; and to develop a research agenda for risk assessment in anaphylaxis. Researchers from the American Academy of Allergy, Asthma & Immunology and the European Academy of Allergology and Clinical Immunology held a PRACTALL (Practical Allergy) meeting to discuss these objectives. New approaches being investigated to support the clinical diagnosis of anaphylaxis include serial measurements of total tryptase in serum during an anaphylaxis episode, and measurement of baseline total tryptase levels after the episode. Greater availability of the test for mature β-tryptase, a more specific mast cell activation marker for anaphylaxis than total tryptase, is needed. Measurement of chymase, mast cell carboxypeptidase A3, platelet-activating factor, and other mast cell products may prove to be useful. Consideration should be given to measuring a panel of mediators from mast cells and basophils. New approaches being investigated to help distinguish sensitized individuals at minimum or no risk from those at increased risk of developing anaphylaxis include measurement of the ratio of allergen-specific IgE to total IgE, determination of IgE directed at specific allergenic epitopes, measurement of basophil activation markers by using flow cytometry, and assessment of allergen-specific cytokine responses. Algorithms have been developed for risk assessment of individuals with anaphylaxis, along with a research agenda for studies that could lead to an improved ability to confirm the clinical diagnosis of anaphylaxis and to identify allergen-sensitized individuals who are at increased risk of anaphylaxis.

Risk assessment in anaphylaxis: current and future approaches

Correct management of anaphylaxis during anaesthesia requires a multidisciplinary approach with prompt recognition and treatment of the acute event by the attending anaesthesiologist, and subsequent determination of the responsible agent(s) with strict avoidance of subsequent administration of all incriminated and/or cross-reacting compounds However, correct identification of the causative compound(s) and safe alternatives is not always straightforward and, too often, not done This review is not intended to discuss acute management of anaesthesia-related anaphylaxis but summarizes the major causes of anaphylaxis during anaesthesia and the diagnostic approach of this rare but potentially life-threatening complication Apart from general principles about the diagnostic approach, history taking and importance of tryptase quantification, more specific confirmatory diagnostic procedures are organized on the basis of the major causes of perioperative anaphylactic reactions

https://faculty.washington.edu/ramaiahr/Review%20Articles/Anapylaxis%20diagnostic%20approach

Anaphylaxis during anaesthesia: diagnostic approach

Mastocytosis consists of a group of disorders characterized by a pathologic increase in mast cells in tissues including skin, bone marrow, liver, spleen, and lymph nodes. Mastocytosis is a rare disease. Because of this, general practitioners have limited exposure to its clinical manifestations, diagnosis, classification, and management. Diagnosis of mastocytosis is suspected on clinical grounds and is established by histopathologic examination of involved tissues such as skin and bone marrow. The most common clinical sign of mastocytosis is the presence of typical skin lesions of urticaria pigmentosa. Most patients experience symptoms related to mast cell mediator release, and prevention of the effects of these mediators on tissues constitutes the major therapeutic goal in the management of mastocytosis. Despite recent advances in knowledge about the pathophysiology, diagnosis, and classification of mastocytosis, a curative treatment for mastocytosis does not now exist. Management of patients within all categories of mastocytosis includes: (1) a careful counseling of patients (parents in pediatric cases) and care providers, (2) avoidance of factors triggering acute mediator release, (3) treatment of acute mast cell mediator release, (4) treatment of chronic mast cell mediator release, and if indicated (5) an attempt to treat organ infiltration by mast cells. The goal of this manuscript is to provide an overview of the mediators produced and released by mast cells, the diagnostic criteria for the different variants of mastocytosis, and the treatment options currently available.

Mastocytosis: current concepts in diagnosis and treatment.

Opioids differ in their capacity to cause release of histamine. The effects of increasing concentrations of three opioids (morphine, buprenorphine, and fentanyl) were studied on the release of preformed (histamine and tryptase) and de novo synthesized (prostaglandin D2 [PGD2] and peptide-leukotriene C4 [LTC4]) chemical mediators from human peripheral blood basophils and mast cells isolated from skin tissues or lung parenchyma. Basophils released < 5% of their histamine content and did not synthesize significant amounts of LTC4 when incubated with any of the opioids. Mast cells showed markedly different responses to the three opioids. Morphine (10(-5)-3 x 10(-4) M), in a concentration-dependent manner, induced histamine and tryptase release from skin but not from lung mast cells, up to a maximum of 18.2 +/- 1.9% and 13.0 +/- 4.1 micrograms/10(7) cells, respectively. Morphine did not induce de novo synthesis of PGD2 from skin mast cells. Buprenorphine (10(-6)-10(-4) M), in a concentration-dependent manner, caused histamine and tryptase release from lung but not from skin mast cells, to a maximum of 47.6 +/- 7.2% and 35.1 +/- 13.6 micrograms/10(7) cells, respectively. Buprenorphine also induced de novo synthesis of PGD2 and LTC4 from lung mast cells. Fentanyl (10(-5)-10(-3) M) did not induce histamine and tryptase release or the de novo synthesis of PGD2 or LTC4 from any mast cells. Histamine release caused by buprenorphine from lung mast cells was slow (t1/2 = 11.2 +/- 3.6 min) compared with that induced by morphine from skin mast cells (t1/2 < 1 min, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Human basophil/mast cell releasability. IX. Heterogeneity of the effects of opioids on mediator release.

Background: The activation of basophils and mast cells plays a role in the pathogenesis of anaphylactoid reactions occurring during the administration of iodinated radiocontrast media. Methods: We compared the effects of three contrast media (CM), Hexabrix (sodium and meglumine salts of ioxaglic acid), Telebrix (sodium and meglumine salts of ioxitalamic acid), and Optiray (ioversol) on the release of preformed (histamine and tryptase) and de novo synthesized (prostaglandin D 2 and leukotriene C 4 ) mediators from human basophils and mast cells isolated from lung, skin, and heart tissue. The commercial preparations were evaluated in parallel with the pure substances. Mannitol was used as a positive control inducing histamine release (HR) by hyperosmolar stimulation. Results: Hexabrix (0.1 to 0.3 mol/L), Telebrix (0.1 to 0.5 mol/L), Optiray (0.2 to 0.5 mol/L), and the corresponding pure substances concentration-dependently induced HR from basophils. A positive correlation was found between CM osmolality and HR from basophils. Mast cells isolated from different anatomic sites responded differently to the three CM. Hexabrix and Optiray induced histamine and tryptase release from human lung mast cells, but not from human skin mast cells. No correlation was found between the osmolality of CM and HR from human lung mast cells. There was a significant correlation between the percent of histamine and tryptase release induced by CM from human lung mast cells. Hexabrix, Telebrix, and Optiray also induced histamine and tryptase release from human heart mast cells. None of the CM induced the de novo synthesis of leukotriene C 4 or prostaglandin D 2 from basophils or mast cells. The kinetics of HR caused by CM differed according to the drug used and the cell (basophils or human lung mast cells) examined. CM-induced HR from basophils and human lung mast cells was temperature-dependent, partially influenced by extracellular Ca 2+ concentrations, and not modified by preincubation of basophils with IL-2 or IL-3. Conclusions: These results provide evidence of the heterogeneity of the effects of CM on mediator release from human basophils and mast cells from different anatomic sites. They also suggest that hyperosmolarity may be an important factor in the activation of basophils by CM, but less relevant for mast cells. CM induce only the release of preformed mediators. The measurement of plasma tryptase might be clinically useful for monitoring adverse reactions caused by CM.

https://www.jacionline.org/article/S0091-6749(96)80162-X/pdf

Human basophil/mast cell releasability. XI. Heterogeneity of the effects of contrast media on mediator release

The authors studied the effects of increasing concentrations (10−5 – 10−3 M) of four muscle relaxants (succinylcholine, d-tubocurarine, vccuronium, and atracurium) on histamine release from peripheral blood basophils and mast cells isolated from human lung parenchyma, skin tissues, and heart fragments. Basophil granulocytes released less than 5% of their histamine content when incubated with any one of the muscle relaxants tested. In contrast, mast cells showed a significant heterogeneity in response to different muscle relaxants. Succinylcholine did not induce histamine release from any type of mast cell, and only high concentrations of d-tubocurarine (10−3 M) caused histamine release from skin and lung mast cells. Vecuronium concentration-dependently induced histamine release from skin and lung—but not from heart mast cells—to a maximum of 7.2 ± 2.1% and 4.9 ± 1.4%, respectively. Atracurium concentration-dependently caused significant histamine release from skin and lung mast cells to a maximum of 46.2 ± 15.1% and 30.6 ± 6.0%, respectively. Atracurium (5 × 10−5 – 2 × 10−4 M) also induced histamine release from heart mast cells. The histamine release process from both lung and skin mast cells caused by atracurium and vecuronium was extremely rapid (t1/2 = < 1 min). The releasing activity of atracurium and vecuronium on lung and skin mast cells was not reduced, and not abolished, by lowering the temperature of the incubation buffer to 22° C and 4° C. Extracellular calcium did not affect the capacity of atracurium and vecuronium to induce histamine release from lung and skin mast cells. The releasing activity of atracurium on lung and skin mast cells was not reduced by metabolic impairment caused by preincubation with 2-deoxy-D-glucose plus antimycin A. Furthermore, this release process was not reduced by preincubation of lung and skin mast cells at 47° C for 20 min. These results confirm that there are functional differences between human basophils and mast cells and among mast cells isolated from different anatomic sites in response to the four muscle relaxants tested.

Heterogeneity of human mast cells and basophils in response to muscle relaxants.

A study was performed about the effects of increasing concentrations of muscle relaxants (suxamethonium, d-tubocurarine, vecuronium, and atracurium), hypnotics (propofol, ketamine, and thiopental), opioids (morphine, buprenorphine, and fentanyl), and benzodiazepines (diazepam, flunitrazepam, and midazolam) on the release of preformed (histamine and tryptase) and de novo synthesized (prostaglandin D2: PGD2 and peptide-leukotriene C4: LTC4) chemical mediators from human basophils and mast cells isolated from skin (HSMC), lung parenchyma (HLMC) and heart tissue (HHMC). None of the drugs tested induced the release of histamine or LTC4 from basophils of normal donors. Suxamethonium did not induce mediator release from any type of human mast cell tested. Only the highest concentration of d-tubocurarine used caused histamine release from HSMC and HLMC. Atracurium, more than vecuronium, induced concentration-dependent histamine release from HSMC and HLMC. Propofol induced a concentration-dependent histamine release from HLMC, but not from HHMC. Only the highest concentrations of ketamine and thiopental used caused a significant release of histamine from HLMC. The muscle relaxants and hypnotics examined did not induce any de novo synthesis of PGD2 or LTC4 in mast cells. Morphine only induced histamine and tryptase release from HSMC, but not the de novo synthesis of PGD2. In contrast, buprenorphine caused histamine and tryptase release from HLMC, and not from HSMC, whilst it also induced de novo synthesis of PGD2 and LTC4 in HLMC. Fentanyl did not give any histamine and tryptase release from mast cells. Diazepam and flunitrazepam only induced a small release of histamine from mast cells, whereas midazolam caused the release of histamine from HLMC. The biochemical pathways underlying the release of mediators from human mast cells induced by drugs used during general anaesthesia are different from those underlying the immune release of histamine. From the results obtained with the in vitro model described here, it is clear that new drugs promising for the anesthesiologic arena should be tested in vitro before their potential histamine-releasing activity is experienced in vivo.

Mechanisms of activation of human mast cells and basophils by general anaesthetic drugs

We have examined the in vitro effects of increasing concentrations of propofol (5–70 μg ml −1 ), ketamine (10 −6 –10 −1 mol litre −1 ) and thiopentone (10 −5 –8 × 10 −4 mol litre −1 ) on the release of preformed histamine and de novo synthesized mediators (peptide leukotriene C 4 (L TC 4 ) or prostaglandin D 2 (PGD 2 ) from human basophils and mast cells isolated from lung parenchyma and skin tissue and from heart fragments. Propofol, ketamine and thiopentone failed to induce the release of histamine and de novo synthesis of LTC4 from basophils. Propofol induced histamine release from lung (mean 8.6 (SEM 1.6)%) and skin mast cells (3.8 (1.5)%), but not from heart mast cells. Ketamine caused release of histamine from lung (6.2 (0.9) %) and skin mast cells (2.5 (1.5) %). Thiopentone caused a small amount of histamine release from lung mast cells (3.1 (1.2)%). Propofol, ketamine and thiopentone did not induce de novo synthesis of PGD 2 and L TC 4 from lung and skin mast cells. These results demonstrate that general anaesthetics induce only histamine release selectively from human mast cells.

Basilio Mazzarella

Papers

Human basophil/mast cell releasability. IX. Heterogeneity of the effects of opioids on mediator release.

Human basophil/mast cell releasability. XI. Heterogeneity of the effects of contrast media on mediator release

Heterogeneity of human mast cells and basophils in response to muscle relaxants.

Mechanisms of activation of human mast cells and basophils by general anaesthetic drugs

General anaesthetics induce only histamine release selectively from human mast cells.