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

NCT01637220 | Completed

• 2 other identifiers: P1109092012-A00242-41
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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 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

Conditions

Anaphylactic Shock to Neuro-Muscular Blocking Agents (NMBA)

Keywords

Anaphylaxis; Neutrophils; Platelet activating factor; Neutrophil Extracellular Traps (NETs)

Outcome Measures

Primary Outcomes (1)

• Percentage of circulating activated neutrophils in the group case compared to that of the group of control.

  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.

  30min post-anaphylactic shock

Secondary Outcomes (3)

• Levels of anti-quaternary ammonium specific IgG in the plasma

  30min post-anaphylactic shock

• Ex vivo activation capacity of blood neutrophils in the presence of neuromuscular blocking drug-IgG immune complexes

  30min post-anaphylactic shock

• Presence of Neutrophil Extracellular Traps in the bronchial aspiration fluid of "cases"

  30min post-anaphylactic shock

Study Arms (1)

case, control

Blood volume collected specifically for this study

Biological: Blood volume collected specifically for this study

Interventions

Blood volume collected specifically for this study BIOLOGICAL

* case patient: 10 ml after the anaphylactic reaction, and during the Allergology-Anesthesia consult 6 to 8 weeks after the shock le choc. * Control patients: 20 ml following neuromuscular blocking drug injection

case, control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Selection of cases : * Any patient of age 18 and over: * Presenting with clinical signs compatible with a perioperative anaphylactic reaction to neuromuscular blocking drugs, whatever the grade of the anaphylactic reaction * That was treated following the French Patient Management 2011 guidelines Selection of controls: * Any patient of age 18 and over * Hospitalized for a surgical intervention necessitating a neuromuscular blocking drug injection, without developing an anaphylactic reaction * That had been informed of the particulars of the study and that had consented to participate in this study

You may qualify if:

• Any patient of age 18 and over:
• Presenting with clinical signs compatible with a perioperative anaphylactic reaction to neuromuscular blocking drugs, whatever the grade of the anaphylactic reaction
• That was treated following the French Patient Management 2011 guidelines

You may not qualify if:

• \- pregnant women
• Selection of controls:
• Any patient of age 18 and over
• Hospitalized for a surgical intervention necessitating a neuromuscular blocking drug injection, without developing an anaphylactic reaction
• That had been informed of the particulars of the study and that had consented to participate in this study

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hospital BICHAT

Paris, 75018, France

Location

Related Publications (1)

• Gouel-Cheron A, de Chaisemartin L, Jonsson F, Nicaise-Roland P, Granger V, Sabahov A, Guinnepain MT, Chollet-Martin S, Bruhns P, Neukirch C, Longrois D; NASA study group. Low end-tidal CO2 as a real-time severity marker of intra-anaesthetic acute hypersensitivity reactions. Br J Anaesth. 2017 Nov 1;119(5):908-917. doi: 10.1093/bja/aex260.

  PMID: 29040433 DERIVED

MeSH Terms

Conditions

Anaphylaxis

Condition Hierarchy (Ancestors)

Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Sylvie Chollet-Martin, MD-PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2012
• First Posted: July 11, 2012
• Study Start: August 1, 2012
• Primary Completion: July 1, 2015
• Study Completion: December 1, 2015
• Last Updated: December 12, 2017

Record last verified: 2017-12

Locations

FR (1)