Paediatric perioperative hypersensitivity: the performance of the current consensus formula and the effect of uneventful anaesthesia on serum tryptase

Nils Vlaeminck; Marie-Line van der Poorten; Cecilie Nygaard Madsen; Birgitte Bech Melchiors; Moïse Michel; Constance Gonzalez; Rik Schrijvers; Jessy Elst; Christel Mertens; Vera Saldien; Joana Vitte; Lene H Garvey; Vito Sabato; Didier G Ebo

doi:10.1016/j.bjao.2023.100254

Paediatric perioperative hypersensitivity: the performance of the current consensus formula and the effect of uneventful anaesthesia on serum tryptase

BJA Open. 2024 Jan 17:9:100254. doi: 10.1016/j.bjao.2023.100254. eCollection 2024 Mar.

Authors

Nils Vlaeminck¹, Marie-Line van der Poorten^{2

3}, Cecilie Nygaard Madsen⁴, Birgitte Bech Melchiors⁴, Moïse Michel^{5

6

7}, Constance Gonzalez⁸, Rik Schrijvers⁹, Jessy Elst², Christel Mertens², Vera Saldien¹, Joana Vitte¹⁰, Lene H Garvey^{4

11}, Vito Sabato², Didier G Ebo^{2

12

13}

Affiliations

¹ Department of Anaesthesiology, Antwerp University Hospital, Belgium.
² Department of Immunology - Allergology - Rheumatology, Antwerp University Hospital, Belgium.
³ Department of Paediatrics, Faculty of Medicine and Health Science, University of Antwerp, Antwerp University Hospital, Belgium.
⁴ Danish Anaesthesia Allergy Centre, Allergy Clinic, Department of Dermatology and Allergy, Copenhagen University Hospital-Herlev and Gentofte, Copenhagen, Denmark.
⁵ Aix-Marseille Université, MEPHI, Marseille, France.
⁶ IHU Méditerranée Infection, Marseille, France.
⁷ CHU Nîmes, Laboratoire d'Immunologie, Nîmes, France.
⁸ Aix-Marseille Univ, University Hospitals of Marseille, Laboratoire d'Immunologie, Marseille, France.
⁹ Department of Microbiology, Immunology and Transplantation, Faculty of Medicine, Allergy and Clinical Immunology Research Group, KU Leuven, Leuven, Belgium.
¹⁰ University of Reims Champagne-Ardenne, INSERM UMR-S 1205 P3CELL and Immunology Laboratory, University Hospital of Reims, Reims, France.
¹¹ Department of Clinical Medicine, University of Copenhagen, Denmark.
¹² Department of Immunology and Allergology, AZ Jan Palfijn Ghent, Ghent, Belgium.
¹³ Infla-Med Centre of Excellence, University of Antwerp, Antwerp, Belgium.

Abstract

Background: Paired sampling of acute (aST) and basal (bST) serum tryptase has been recommended when investigating patients with a suspected perioperative hypersensitivity (POH) reaction. In the current consensus formula, an aST value exceeding (1.2×bST+2) confirms mast cell activation. The current consensus formula has been validated in adults but not in children.

Methods: We prospectively included 96 children who underwent uneventful anaesthesia and sampled serum tryptase at baseline and 60-90 min after induction. Tryptase changes were then compared with those in 94 children with suspected POH who were retrospectively included from four reference centres in Belgium, France, and Denmark.

Results: We observed a median decrease in serum tryptase during uneventful anaesthesia of 0.41 μg L^-1 (-15.9%; P<0.001). The current consensus formula identified mast cell activation in 31.9% of paediatric POH patients. After generating receiver operating characteristic curves through 100 repeated five-fold cross-validation, aST>bST+0.71 was identified as the optimal cut-off point to identify mast cell activation. This new paediatric formula has higher sensitivity than the current consensus formula (53.2% vs 31.9%, P<0.001) with a specificity of 96.9%. Analysis in the subpopulation where a culprit was identified and in grade 3-4 reactions similarly yielded higher sensitivity for the new paediatric formula when compared with the current consensus formula (85.3% vs 61.8%; P=0.008 and 78.0% vs 48.8%; P<0.001, respectively). Internally cross-validated sensitivity and specificity were 53.3% and 93.3%, respectively.

Conclusions: This is the first study suggesting the need for an adjusted formula in children to identify perioperative mast cell activation as tryptase is significantly lowered during uneventful anaesthesia. We propose a new formula (aST>bST+0.71) which performs significantly better than the current consensus formula in our multicentric paediatric population.

Keywords: Formula for mast cell activation in children; POH diagnosis; Paediatric POH; Paired serum tryptase; Performance of consensus formula; Perioperative anaphylaxis; Perioperative hypersensitivity; Uneventful anaesthesia.