Rates and types of urine drug screen false negative results compared with confirmatory toxicology testing in major trauma patients

Trauma centers are required to screen patients for alcohol use, and if necessary, intervene and refer to treatment (SBIRT). Similar screening for illicit drug use is recommended but not required. Urine drug screening (UDS) underestimates problematic substance use. This study aimed to estimate the types and rates of UDS false negatives (FN) compared to comprehensive testing by liquid chromatography-mass spectrometry (LC-MS) in trauma patients. We performed a prospective cohort study of deidentified urine samples from adult trauma and burn activation patients. Both UDS and LC-MS comprehensive testing of &gt;200 analytes were performed by a reference laboratory on all samples. Iatrogenic medications were excluded from the FN count. Crosstab analyses were conducted for UDS versus LC-MS outcomes to establish FN types and rates. We dichotomized the results by creating an “intentionality” variable (intentional injuries by self/others versus accidental injuries). A series of crosstabs with odds ratios considered intentionality by substance class and demographics. Statistically significant variables by Chi-Square were assessed by logistic regression. Psychoactive FN were detected in 56/100 urine samples analyzed; the most frequent included anticonvulsants (primarily gabapentin, <i>N</i> = 13), opioid agonists (<i>N</i> = 12), antihistamines (primarily diphenhydramine, <i>N</i> = 10), and phenethylamines (primarily bupropion, <i>N</i> = 5). Nonpsychoactive FN were detected in 70/100 samples; the most common were nicotine (<i>N</i> = 33), caffeine (<i>N</i> = 23), acetaminophen (<i>N</i> = 22), and antidepressants (<i>N</i> = 12). Of substance classes included in the UDS and also tested by LC-MS, FN occurred for opiates (3%), amphetamines (5%) and opioids (25%). Polypharmacy was associated with fall injuries in elderly patients. Cocaine (<i>p</i> = 0.015) and cannabinoids (<i>p</i> = 0.002) were significantly associated with intentionality. Our results indicate that FN for potentially important psychoactive and nonpsychoactive substances are common when toxicologic testing is limited to routine UDS in trauma patients. We recommend expanding SBIRT in this patient population to include misuse of tobacco products, prescription analgesics, and over-the-counter antihistamines.

创伤中心需对患者进行酒精使用筛查，必要时需采取干预措施并转诊至治疗机构（Screening, Brief Intervention, and Referral to Treatment, SBIRT）。针对非法药物使用的类似筛查虽有推荐，但并非强制要求。尿液药物筛查（Urine Drug Screening, UDS）会低估存在问题的物质使用情况。本研究旨在对比液相色谱-质谱联用法（Liquid Chromatography-Mass Spectrometry, LC-MS）的全面检测结果，估算创伤患者尿液药物筛查假阴性（False Negatives, FN）的类型与发生率。我们对成年创伤及烧伤接诊患者的去标识化尿液样本开展了前瞻性队列研究。所有样本均由参考实验室同时完成UDS检测及针对200余种分析物的LC-MS全面检测。本研究将医源性用药排除在假阴性计数范围之外。针对UDS与LC-MS的检测结果开展列联表分析，以明确假阴性的类型与发生率。我们通过构建“故意性”变量对结果进行二分类：即由自身或他人造成的故意伤害与意外损伤。随后开展一系列带有优势比的列联表分析，按物质类别与人口统计学特征探讨“故意性”的相关关联。经卡方检验筛选出的具有统计学显著性的变量，进一步通过逻辑回归进行验证分析。在本次分析的100份尿液样本中，共检出56份存在精神活性物质假阴性情况，其中最常见的类别为抗惊厥药（主要为加巴喷丁，N=13）、阿片受体激动剂（N=12）、抗组胺药（主要为苯海拉明，N=10）以及苯乙胺类物质（主要为安非他酮，N=5）。另有70份样本检出非精神活性物质假阴性，其中最常见的为尼古丁（N=33）、咖啡因（N=23）、对乙酰氨基酚（N=22）及抗抑郁药（N=12）。在UDS检测覆盖且LC-MS也完成检测的物质类别中，阿片类（3%）、苯丙胺类（5%）及阿片类药物（25%）出现了假阴性情况。多重用药与老年患者的跌倒损伤存在显著关联。可卡因（p=0.015）及大麻素类（p=0.002）与故意伤害行为存在显著关联。本研究结果表明，若创伤患者的毒理学检测仅局限于常规UDS，检出具有临床重要性的精神活性与非精神活性物质假阴性的情况十分普遍。我们建议在该患者群体中拓展SBIRT服务范畴，将烟草产品滥用、处方类镇痛药及非处方抗组胺药纳入筛查内容。