苯海拉明剂量反应：一种确定分诊阈值的新方法。

Diphenhydramine dose-response: a novel approach to determine triage thresholds.

机构信息

New Mexico Poison & Drug Information Center, University of New Mexico, Albuquerque, NM 87131-0001, USA.

出版信息

Clin Toxicol (Phila). 2010 Oct;48(8):820-31. doi: 10.3109/15563650.2010.514269.

DOI:10.3109/15563650.2010.514269

PMID:20969503

Abstract

CONTEXT

It is unclear how much diphenhydramine (DPH) is toxic in humans. Previous dose-response studies have had conflicting results. Objective. We sought to evaluate DPH dose-response using a unique method that utilizes acetaminophen (APAP) serum concentrations to estimate DPH doses in patients ingesting APAP/DPH in a fixed-combination product.

METHODS

We retrospectively analyzed APAP/DPH-only exposures in patients 2-80 years of age using case data from 15 U.S. poison centers. DPH dose was extrapolated from measured serum APAP concentrations. A clinically significant response (CSR) was predefined in terms of eight specific manifestations (e.g., coma) that would warrant emergency department intervention. Nominal logistic regression was used to model the probability of each recorded manifestation across DPH dose ranges examining fits for mg, mg/kg, log10 mg, and log10 mg/kg DPH doses. The threshold value where patients reliably became symptomatic was determined by further examining receiver operating characteristic curves.

RESULTS

There were 509 cases that met inclusion criteria. Forty-five patients (9%) developed CSRs. A higher percentage of patients developed CSR at ≥ 7.5 mg/kg DPH and ≥1 g total DPH cutoff points (p < 0.05, Fisher's exact test). The best model for predicting the probability of CSR was a logistic fit of log(10) mg/kg dose (p < 0.05). By this model, for every 1 log(10) unit increase of mg/kg DPH dose, the odds of developing a CSR increased 47-fold (95% CI 17, 154). Receiver operating characteristic analyses showed a dose-related progression of symptoms. The cut-point with greatest sensitivity (98%) versus 1-specificity (57%) corresponded to an extrapolated mg/kg DPH dose of 8.2 mg/kg (95% CI 5.6, 10.5).

CONCLUSION

Our findings support the current American Association of Poison Control Centers' guideline recommendation to refer patients to the hospital for evaluation if they have ingested greater than or equal to 7.5 mg/kg of DPH.

摘要

背景

目前尚不清楚人类摄入多少剂量的苯海拉明（DPH）会产生毒性。先前的剂量反应研究结果相互矛盾。目的：我们试图使用一种独特的方法评估 DPH 剂量反应，该方法利用对乙酰氨基酚（APAP）血清浓度来估计摄入含有 APAP/DPH 的固定复方产品的患者中的 DPH 剂量。

方法

我们使用来自美国 15 个中毒中心的病例数据，对 2-80 岁的仅摄入 APAP/DPH 的患者进行了回顾性分析。DPH 剂量是从测量的血清 APAP 浓度推断出来的。根据需要急诊干预的八个具体表现（如昏迷），将临床显著反应（CSR）定义为一个预定义的终点。名义逻辑回归用于对每个记录表现的概率进行建模，跨越 DPH 剂量范围，检查 mg、mg/kg、log10mg 和 log10mg/kg DPH 剂量的拟合情况。通过进一步检查受试者工作特征曲线，确定患者可靠出现症状的阈值值。

结果

共有 509 例符合纳入标准。45 例（9%）患者出现 CSR。在 DPH 剂量≥7.5mg/kg 和总 DPH 剂量≥1g 的截定点，出现 CSR 的患者比例更高（p<0.05，Fisher 精确检验）。预测 CSR 发生概率的最佳模型是 log（10）mg/kg 剂量的逻辑拟合（p<0.05）。根据该模型，DPH 剂量每增加 1 log（10）单位，发生 CSR 的几率增加 47 倍（95%CI 17，154）。受试者工作特征分析显示症状呈剂量相关性进展。具有最大敏感性（98%）和 1 特异性（57%）的截定点对应于推断的 mg/kg DPH 剂量 8.2mg/kg（95%CI 5.6，10.5）。