福可定暴露增加了围手术期对神经肌肉阻滞剂过敏反应的风险：ALPHO 病例对照研究。
Pholcodine exposure increases the risk of perioperative anaphylaxis to neuromuscular blocking agents: the ALPHO case-control study.
机构信息
Department of Anesthesia and Intensive Care, Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil, INSERM U1255, FMTS de Strasbourg, Strasbourg, France.
Nancy Regional University Hospital Center, Regional Pharmacovigilance Center of Nancy, Vandoeuvre-lès-Nancy, France.
出版信息
Br J Anaesth. 2023 Jul;131(1):150-158. doi: 10.1016/j.bja.2023.02.026. Epub 2023 Mar 24.
BACKGROUND
Neuromuscular blocking agents (NMBAs) are among the leading cause of perioperative anaphylaxis, and most of these reactions are IgE mediated. Allergic sensitisation induced by environmental exposure to other quaternary ammonium-containing compounds, such as pholcodine, has been suggested. The aim of this study was to assess the relationship between pholcodine exposure and NMBA-related anaphylaxis.
METHODS
ALPHO was a multicentre case-control study, comparing pholcodine exposure within a year before anaesthesia between patients with NMBA-related perioperative anaphylaxis (cases) and control patients with uneventful anaesthesia in France. Each case was matched to two controls by age, sex, type of NMBA, geographic area, and season. Pholcodine exposure was assessed by a self-administered questionnaire and pharmaceutical history retrieved from pharmacy records. The diagnostic values of anti-pholcodine and anti-quaternary ammonium specific IgE (sIgE) were also evaluated.
RESULTS
Overall, 167 cases were matched with 334 controls. NMBA-related anaphylaxis was significantly associated with pholcodine consumption (odds ratio 4.2; 95% confidence interval 2.3-7.0) and occupational exposure to quaternary ammonium compounds (odds ratio 6.1; 95% confidence interval 2.7-13.6), suggesting that apart from pholcodine, other environmental factors can also lead to sensitisation to NMBAs. Pholcodine and quaternary ammonium sIgEs had a high negative predictive value (99.9%) but a very low positive predictive value (<3%) for identifying NMBA-related reactions.
CONCLUSIONS
Patients exposed to pholcodine 12 months before NMBA exposure have a significantly higher risk of an NMBA-related anaphylaxis. The low positive predictive values of pholcodine and quaternary ammonium sIgEs precludes their use to identify a population with a high risk of NMBA-related anaphylaxis.
CLINICAL TRIAL REGISTRATION
NCT02250729.
背景
神经肌肉阻滞剂（NMBAs）是围手术期过敏反应的主要原因之一，其中大多数反应是 IgE 介导的。有人提出，环境暴露于其他季铵类化合物（如福可定）会引起过敏致敏。本研究旨在评估福可定暴露与 NMBA 相关过敏反应之间的关系。
方法
ALPHO 是一项多中心病例对照研究，比较了法国麻醉前一年内接受 NMBA 相关围手术期过敏反应（病例）和未发生麻醉并发症的对照患者之间的福可定暴露情况。每个病例通过年龄、性别、NMBA 类型、地理区域和季节与两名对照匹配。福可定暴露情况通过自我管理问卷和从药房记录中检索的药物史进行评估。还评估了抗福可定和抗季铵特异性 IgE（sIgE）的诊断价值。
结果
总体而言，167 例病例与 334 例对照相匹配。NMBA 相关过敏反应与福可定消耗显著相关（比值比 4.2；95%置信区间 2.3-7.0）和职业暴露于季铵化合物（比值比 6.1；95%置信区间 2.7-13.6），这表明除了福可定之外，其他环境因素也可能导致对 NMBA 的致敏。福可定和季铵 sIgE 具有很高的阴性预测值（99.9%），但对识别 NMBA 相关反应的阳性预测值很低（<3%）。
结论
在 NMBA 暴露前 12 个月暴露于福可定的患者发生 NMBA 相关过敏反应的风险显著增加。福可定和季铵 sIgE 的低阳性预测值排除了其用于识别 NMBA 相关过敏反应风险较高的人群的可能性。
临床试验注册
NCT02250729。
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