Role of Neutrophil Activation in Anaphylaxis to Neuro-Muscular Blocking Agents (NASA)
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|ClinicalTrials.gov Identifier: NCT01637220|
Recruitment Status : Completed
First Posted : July 11, 2012
Last Update Posted : December 12, 2017
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).
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 after the shock perform, 1) cutaneous tests to NMBA, 2) a study of the capacity of stimulation of ex vivo neutrophils by IgG- NMBA complexes
|Condition or disease||Intervention/treatment|
|Anaphylactic Shock to Neuro-Muscular Blocking Agents (NMBA)||Biological: Blood volume collected specifically for this study|
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|Study Type :||Observational|
|Actual Enrollment :||200 participants|
|Official Title:||Role of Neutrophil Activation in Anaphylaxis to Neuro-Muscular Blocking Agents|
|Study Start Date :||August 2012|
|Actual Primary Completion Date :||July 2015|
|Actual Study Completion Date :||December 2015|
Blood volume collected specifically for this study
Biological: Blood volume collected specifically for this study
- Percentage of circulating activated neutrophils in the group case compared to that of the group of control. [ Time Frame: 30min post-anaphylactic shock ]This measure will be based on the intensity of expression of the activation marker CD62L (L-selectin) by blood neutrophils using flow cytometry. Our preliminary data indicate that the Mean Fluorescence Intensity (MFI) of CD62L is >450 when considering " non-activated " neutrophils, and CD62L(MFI)<300 when considering " activated " neutrophils.
- Levels of anti-quaternary ammonium specific IgG in the plasma [ Time Frame: 30min post-anaphylactic shock ]the group case compared to the group of control.
- Ex vivo activation capacity of blood neutrophils in the presence of neuromuscular blocking drug-IgG immune complexes [ Time Frame: 30min post-anaphylactic shock ]the group case compared to the group of control.
- Presence of Neutrophil Extracellular Traps in the bronchial aspiration fluid of "cases" [ Time Frame: 30min post-anaphylactic shock ]the group case compared to the group of control.
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Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01637220
|Paris, France, 75018|
|Principal Investigator:||Sylvie Chollet-Martin, MD-PhD||Assistance Publique - Hôpitaux de Paris|