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Role of Neutrophil Activation in Anaphylaxis to Neuro-Muscular Blocking Agents

Assistance Publique - Hôpitaux de Paris · 2012
ClinicalTrials.gov · Datasets · License: Public Domain · 2012
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In about 10% of preoperative anaphylactic reactions to Neuro-Muscular Blocking Agents (NMBA) (114 patients analyzed at the BICHAT Hospital), a classical mechanism (mast cell- and IgE-dependent) is not identified. The mechanisms underlying these atypical anaphylactic reactions are unknown. The investigators have developed at the Pasteur Institute a murine model of anaphylaxis in which neutrophils, IgG and Platelet Activating Factor (PAF) play predominant roles. In addition, preliminary results obtained at the BICHAT Hospital suggest the presence of specific IgG anti-quaternary ammonium in the sera of patients that had developed a shock to NMBA anesthesia, but not in controls exposed to NMBA anesthesia or in normal blood donors. Finally, the release of neutrophil extracellular traps (NETs), extracellular filaments made of DNA and histones, may contribute to respiratory symptoms HYPOTHESIS: Neutrophils are implicated in NMBA -induced anaphylactic reactions in humans. Activated by IgG-NMBA complexes, which aggregate IgG receptors, neutrophils release PAF and NETs that are implicated in the cardiac and respiratory distress during anaphylaxis. It is possible that the activation of neutrophils: 1) explains the clinical features of atypical anaphylactic reactions (non-IgE mediated), 2) participates also in part to classical anaphylactic reactions GENERAL OBJECTIVE: Compare the percentage of circulating activated neutrophils in a group of patients immediately following a NMBA -induced shock (case) to that of a group of patients exposed to NMBA during anesthesia without developing a shock (control). SECONDARY OBJECTIVES: A) the day of the shock, quantify and compare between case and controls, 1) the level of circulating anti-quaternary ammonium IgG by immuno fluorometry, 2) the expression of IgG receptors (FcR) on the surface of neutrophils by cytometry, 3) the levels of circulating PAF by mass spectrometry, 4) the amount of NETs by immunofluorescence. B) 6 to 10 weeks aft
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