The Urine Drug Screen - Know Thy Limitations

We are all guilty of ordering them in the ED, but do we really know what we’re ordering?

Urine Sample. By Turbotorque (Own work) [Public domain], via Wikimedia Commons

The Implications of the Urine Drug Screen

1 literature review looked at 7 different retrospective studies describing a total of 1,405 patients and found the urine drug screen did not affect the management of any of these patients while in the emergency department (Tenenbein M., 2009).  However, the data from the UDS can affect a patient’s clinical care outside of the Emergency Department.  For example, if a patient requires psychiatric inpatient care, initial knowledge of drug abuse could affect this patient’s etiology of illness or rehabilitation plan.

The UDS in the ED is Qualitative
It’s typically an immunoassay, in which you have a specific antibody designed to attach to a specific antigen (either the drug or a metabolite).  You’re going to get a positive or a negative result.

The Positive Result

• A positive result means that the derivative of the drug tested in the immunoassay was found and reached its threshold of detection.
• You can assume exposure either to the drug tested, or to a substance with a similar chemical structure that has cross-reacted with the immunoassay.
• It cannot tell you the specific drug taken or the amount.  
• It cannot tell you if the drug is causing your patient’s current symptoms, since the UDS often remains positive for a greater duration than any clinical effects of the drug.  That suspected overdose causing altered mental status can always still be a head bleed.

The Negative Result

• A negative result means that the derivative of the drug being tested in the immunoassay was either absent or no longer accumulated enough to reach the threshold for a positive result.
• This does not mean it or another version of a drug is present.  If you suspect drug use, trust your gut.

The Basic Urine Drug Screen

It’s important to understand the drug assay your ED uses and its limitations.  For a basic UDS, let’s go over a few broad limitations one might encounter:

Amphetamines

• A basic amphetamine screen is unlikely to detect MDMA, designer drugs, or LSD.
•  Many common nasal inhalers, decongestants (i.e. pseudoephedrine), antipsychotics, stimulant ADD/ADHD medications (i.e, methylphenidate), and antidepressants (i.e. trazodone and buproprion) may also give you a false positive.

Benzodiazepines

• Many basic urine drug screens only test for the breakdown metabolites, oxazepam and noroxazepam.
• Alprazolam (Xanax), clonazepam (Klonopin), lorazepam (Ativan), midazolam (Versed), and triazolam (Halcyon) do not undergo metabolism to oxazepam and can be missed in detection.  
• Sertraline can also commonly cause false positives.
• One helpful mnemonic for some of the benzos picked up by the UDS: The benzo screen TOLD me about my patient’s benzo use:

    T - temazepam
    O - oxazepam
    L - Librium (chlordiazepoxide)
    D - diazepam

Opiates
‘Opiate’ is the broad term used to define the natural opioids, as opposed to the umbrella term ‘opioid’, which is generally used to describe the ‘natural’, semi-synthetic, and synthetic xenobiotics that act at the mu receptor.  When you see the ‘t,’ think of morphine, codeine, which both are naturally isolated from the opium poppy (Papaver somniferum), and heroin (metabolizes into morphine).  This does not include the semisynthetic and synthetic types of opioids our patients have access to.  The UDS is unlikely to detect semisynthetics, like oxycodone, hydrocodone as the molecular structures are too altered from the natural opiate.  It will not detect synthetics like fentanyl or methadone, as the structures are too dissimilar, unless your hospital’s UDS specifically tests for these xenobiotics.

• It is possible to obtain a false positive from poppy seeds if eaten in large amounts.
• Ofloxacin and levofloxacin may also create false positive results. 

Chemical Structure of Morphine. By NEUROtiker (Own work) [Public domain], via Wikimedia Commons

Chemical Structure of Fentanyl.  By Ben Mills (Own work) [Public domain], via Wikimedia Commons

THC

• The synthetic cannabinoids (Spice, K2, ‘fake weed’), which have become increasingly more frequent, will not be picked up on a THC screen.

PCP

• One can see false positives from a number of commonly used substances includingdiphenhydramine, ibuprofen, dextromethorphan, venlafaxine, and lamotrigine.

So what should I do?

• First, reach out to your facility’s lab and learn about the capabilities of its urine drug screen.   There are many different types of drug screens, and each varies in their false positives.  Knowing the limitations of your institutions UDS will help you safely interpret the data you obtain when ordering it. 
• Second, trust your clinical gestalt.  If you suspect your patient is abusing substances, then don’t let a urine sample talk you out of it.  As you know now, it’s not perfect. 
• Third, listen to your patient – most are going to be just as reliable as their urine (Perrone J, et al, 2001).

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References

• Tenenbein M. Do you really need that emergency drug screen? Clin Toxicol (Phila). 2009 Apr;47(4):286-91. doi: 10.1080/15563650902907798. Review. PubMed PMID: 19514875.
• Alec Saitman, Hyung-Doo Park, and Robert L. Fitzgerald. False-Positive Interferences of Common Urine Drug Screen Immunoassays: A Review.  J Anal Toxicol (2014) 38 (7): 387-396 first published online July 1, 2014 doi:10.1093/jat/bku075.
• Baker JE, Jenkins AJ. Screening for cocaine metabolite fails to detect an intoxication. Am J Forensic Med Pathol. 2008 Jun;29(2):141-4. doi: 10.1097/PAF.0b013e318174e7ab. PubMed PMID: 18520481.
• Cone EJ, Caplan YH, Black DL, Robert T, Moser F. Urine drug testing of chronic pain patients: licit and illicit drug patterns. J Anal Toxicol. 2008 Oct;32(8):530-43. PubMed PMID: 19007501.
• Perrone J, De Roos F, Jayaraman S, Hollander JE. Drug screening versus history in detection of substance use in ED psychiatric patients. Am J Emerg Med. 2001 Jan;19(1):49-51. PubMed PMID: 11146019.
• Rengarajan A, Mullins ME. How often do false-positive phencyclidine urine screens occur with use of common medications? Clin Toxicol (Phila). 2013 Jul;51(6):493-6. doi: 10.3109/15563650.2013.801982. Epub 2013 May 23. PubMed PMID: 23697457; PubMed Central PMCID: PMC4384887.

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Thanks to Dr. Gillian Beauchamp, former CincyEM resident and current toxicology fellow at Oregon Health Sciences University for providing pre-publication review.