Etomidate Does Not Cause False-Positive Benzodiazepine Results on Urine Drug Screens
Etomidate, a short-acting intravenous anesthetic agent, is not known to cause false-positive results for benzodiazepines on urine drug screening (UDS). There is no evidence in the medical literature documenting cross-reactivity between etomidate and benzodiazepine immunoassays.
Evidence Review
The comprehensive literature on false-positive UDS results does not identify etomidate as a cause of benzodiazepine screen interference:
A systematic review of false-positive interferences with UDS immunoassays covering literature from 2000 onward identified multiple causes of false-positive results for amphetamines, opiates, benzodiazepines, cannabinoids, and other drug classes, but etomidate was not mentioned as a cross-reactive substance 1
A large-scale analysis using electronic health records to discover cross-reactivity in UDS immunoassays through 698,651 UDS results across 10 assays systematically identified cross-reactive medications, but etomidate was not identified as causing benzodiazepine false-positives 2
A comprehensive review of commonly prescribed medications and potential false-positive UDS results identified 25 reports of false-positive results across multiple drug classes, but etomidate was not among the medications associated with benzodiazepine false-positives 3
Clinical Context
While etomidate is chemically distinct from benzodiazepines, it does share some pharmacologic properties:
Etomidate is a sedative-hypnotic agent used for rapid sequence intubation, but its chemical structure (an imidazole derivative) is completely different from benzodiazepines (which contain a benzene ring fused to a diazepine ring) 4
The absence of structural similarity makes cross-reactivity with benzodiazepine immunoassays highly unlikely from a biochemical standpoint 1
Important Caveats When Interpreting Benzodiazepine UDS Results
If you encounter a positive benzodiazepine screen in a patient who received etomidate, consider these alternative explanations:
Many benzodiazepines are not reliably detected by standard screens: Clonazepam and lorazepam may not be detected by standard benzodiazepine screens that primarily identify oxazepam 5
Designer benzodiazepines cause true positives: Non-FDA-approved benzodiazepines (flubromazolam, flualprazolam, etizolam, clonazolam) are increasingly common and will trigger positive screens but may not be confirmed by standard LC-MS-MS panels 6
Confirmatory testing is essential: Standard immunoassay screening tests are presumptive only and require confirmation by gas chromatography-mass spectrometry (GC-MS) when results are unexpected or will impact clinical decisions 5, 7
Always obtain complete medication history: Ask specifically about all prescribed benzodiazepines, over-the-counter medications, and supplements before interpreting any positive result 7
Recommended Approach
When encountering a positive benzodiazepine screen in a patient who received etomidate:
Do not attribute the positive result to etomidate - look for other explanations including actual benzodiazepine use (prescribed or illicit), designer benzodiazepines, or laboratory error 5, 3
Order confirmatory testing with GC-MS before making any clinical decisions that could adversely affect the patient 5, 7
Consult with your laboratory toxicologist to discuss unexpected results and determine if expanded testing for designer benzodiazepines is warranted 5, 7
Never make punitive decisions based solely on immunoassay screening results without confirmatory testing 7