Background: Interpretation of TCA urine immunoassays is confounded by frequent false positive results, often leading to problematic interpretation. Although clinical evaluation of TCA toxicity is most important, increased specificity of these frequently ordered tests would be helpful. We compare two TCA immunoassays with cutoffs of 1000ng/mL (SureStep by Applied Biotech, Inc., and Triage Drags of Abuse Panel by Biosite Diagnostics) with our existing immunoassay (EMIT by Syva, cutoff 300 ng/mL nortriptyline) to determine if the increased threshold is sufficient to decrease false positive results. We also investigate the ability of these assays to identify patients with clinical TCA toxicity. Methods: Adult patients with positive TCA urine assays by EMIT who had stored urine were included in the study. A retrospective chart review was performed, abstracting data for toxicants and clinical evidence of TCA toxicity (hypotension, tachycardia, altered mental status, anticholinergic toxidrome). Available EKGs were reviewed for evidence of abnormal terminal R wave in lead a VR and QRS duration. Results: 66 patients met inclusion criteria. 3 patients demonstrated clinical evidence of TCA toxicity. Both higher cutoff assays detected these 3. Positive predictive values were 4.5%, 12% and 13% for the EMIT, Biosite and Applied Biotech assays respectively. Specificity (95% confidence intervals) was 65% (52-78%) and 68% (56-80%) for the SureStep and Triage assays, respectively. Conclusions: Utilizing a TCA immunoassay with a cutoff of 1000ng/mL maintains sensitivity for TCA overdose, while eliminating more than 1/2 of the false positive results in this patient population. Further study may support the use of low and high threshold testing combined with clinical presentation to suggest the presence of TCA immunoassay cross-reactants., Gee A, McKay CA, Wu, AHB. Hartford Hospital/ UCONN School of Medicine, Hartford, [...]