MRGPRX2 Triggers rocuronium bromide-induced peri-operative phase allergic shock: A case report with case control study.

BACKGROUND

Activation of mast cells and systemic histamine release are major side effects of intravenously administered neuromuscular blocking agents (NMBAs). Mas-related G protein-coupled receptor-X2 (MRGPRX2) plays a key role in mediating anaphylactoid reactions.

OBJECTIVE

To explore the mechanism of acute anaphylactic shock induced by muscle relaxants through the typical shock cases.

DESIGN

Case report and case control study.

PATIENTS

A 68-year-old male patient (80 kg) underwent surgical treatment in September 2023 and developed anaphylactic shock during anaesthesia induction.

METHODS

A trial was conducted to evaluate the patient who experienced anaphylactic shock during the peri-operative period in comparison to control patients. The levels of MRGPRX2 and total immunoglobulin E (IgE) were measured in patient plasma, along with allergic mediators such as histamine and tryptase. Mast cell activation assay was performed to assess degranulation effectiveness by measuring β-hexosaminidase, histamine release, and calcium influx. Additionally, mast cell activation by peri-operative drugs was investigated. Local inflammatory experiments were conducted in a mouse model to evaluate rocuronium bromide-induced allergic reactions. Finally, MRGPRB2-CKO mice and siRNA silencing were used to elucidate the mechanism of rocuronium-induced anaphylactic shock.

RESULTS

Plasma analysis of the patient experiencing anaphylaxis revealed normal total IgE levels (38.4 IU ml-1) but significantly elevated histamine concentration (53.78 ng ml-1). The MRGPRX2 concentration (52.22 ng ml-1) in this patient was markedly higher than the negative control group (16.40 ng ml-1). Serum-activated mast cell assays demonstrated that the anaphylaxis patient's plasma induced a significant release of β-hexosaminidase, calcium, and histamine from mast cells (significantly higher than the histamine levels naturally present in the plasma). Drug-activated mast cell experiments confirmed that rocuronium bromide triggered dose-dependent mast cell activation, leading to MCP-1, histamine, and calcium release. Local paw oedema experiments in mice further validated that rocuronium bromide induced local allergic reactions. Using MRGPRB2-CKO mice and siRNA silencing, we determined that rocuronium bromide-induced anaphylactic shock was mediated through MRGPRX2 activation, resulting in mast cell degranulation.

CONCLUSION

This study highlights the critical role of MRGPRX2 in rocuronium bromide-induced anaphylactic shock. In vitro diagnosis of MRGPRX2 levels may provide new criteria for reducing intra-operative risks.

TRIAL REGISTRATION

The clinical trial was registered at the China Clinical Trial Registration Center (Registration Number: ChiCTR2300077364).