The Urine Screen: How Reliable is it Really?

Before you put too much weight on a positive or negative urine drug screen, familiarize yourselves with its limitations: Timing of exposures, false positives and the multitude of drugs that can be missed.

The Case
A 23-year-old woman presents to your ED with sluggish pupils and slurred speech. You try Narcan without effect. A friend arrives and tells you she drank vodka and took some unknown pills. Her urine drug screen comes back positive for methadone, amphetamines and PCP. What did she take? It may have been methadone, amphetamines, and PCP, but it also could have been a combination of over-the-counter and prescription medications such as doxylamine, bupropion, and diphenhydramine.

Background
The urine drug screen (UDS) is a commonly used test in the emergency department for patients who are symptomatic from a possible overdose, have altered mental status of unknown etiology, and often for asymptomatic patients who require “medical clearance” for a psychiatric evaluation. But how much trust should we put in a positive or negative UDS? Goldfrank’s Toxicological Emergencies describes the major problems with the UDS as “issues of poor sensitivity and specificity, poor correlation with clinical effects, and infrequent alteration of patient management [1].” This is not to say the UDS has no clinical utility. When used in the right clinical contexts, and when the results will help guide management or future care, it can certainly be helpful. Drug screens have been found to only rarely impact ED management of patients [2]. However, particularly in trauma patients, it may be helpful for substance abuse counselling that typically occurs as an inpatient on trauma wards. Also, in pediatric patients when there are unusual mental status changes and a possible overdose, it can be useful. ACEP has a clinical policy stating that a routine UDS is NOT recommended for awake, alert, patients who can cooperate with their care, as it rarely impacts treatment, and can cause significant delays in time to treatment and definitive management.
There are three major problems with the UDS: timing of exposures, false positives, and many drugs that are missed or not detected.

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1. Time lag
A positive UDS may represent an exposure several days to weeks prior that may have no relation to the current presentation or symptoms. For example, amphetamines, barbiturates, cannabinoids, cocaine, and opiates can all remain positive for up to four days. Phencyclidine and cannabinoids can be positive up to one month in cases of heavy or prolonged use, benzodiazepines and phenobarbital even with routine use can remain positive for one month! This means that the patient who has chest pain and screens positive for cocaine may have used cocaine that day and triggered vasospasm and cardiac ischemia, but it could be due to use several days prior. Obtaining a good history is important to sort out the timing of exposure and symptom onset. The catch-22 is that drug abuse history is, unfortunately, often unreliable.

2. Cross-reactivity
Certain prescription and over-the-counter medications can interact and produce a “false positive” tox screen. Table 1 (click to enlarge) lists many of the false positives that we should be aware of [1,3-6]. For example, false positives for amphetamines can arise from bupropion metabolites, decongestants, ephedrine, methamphetamine, and selegiline. There are also case reports of reactivity with labetalol and metformin. Interestingly, methylphenidate does not typically trigger a positive amphetamine assay [7], though this may vary by the assay used in an individual lab. Quinolones can cross react with the opiate assay, as can naloxone, creatine, and verapamil. Doxylamine can cross react with the methadone assay. A positive PCP reading could be from dextromethorphan, diphenhydramine, venlafaxine, tramadol or ketamine. False positive cannabinoid screens can arise from NSAIDs such as ibuprofen and naproxen, as well as the anti-retroviral, efavirenz. However, this has not been found consistently across all studies. The frequency of crossover, however, is not well defined.

3. Non-detection
Numerous drugs of abuse are not tested for on the typical urine drug screen or have low and variable reactivity. For example, the opioid screen reacts with morphine, oxycodone, and codeine, but synthetic opioids such as fentanyl, methadone, and tramadol have little reactivity on the opioid urine screen. Drugs of abuse such as synthetic cannabinoids (also called K2 or spice), bath salts, and gamma-hydroxybutyrate (GHB), all of which can cause significant neuro-psychiatric side effects, are unfortunately not detected with a typical drug screen as well. Drug screens available in the ED will also vary by site and lab capabilities. Some drug screens test for methadone, separately, so would detect it even if the opiate screen is negative. Commonly tested drugs include opiates, cannabinoids, benzodiazepines, barbiturates, cocaine, PCP, and amphetamines. For all the reasons described above, the UDS results alone should not drive management. Often there are multiple substances that have been used or ingested simultaneously, and treatment should be driven by the symptom presentation. A knowledge of the limitations and utility of the UDS is critical for using and interpreting it wisely.

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REFERENCES

1. Rainey PM. Laboratory principles. In: Hoffman RS, Howland M, Lewin NA, Nelson LS,  Goldfrank LR, eds. Gaoldfrank’s toxicologic emergencies. 10th ed. New York, NY: McGraw-Hill; 2015. Accessed 10/2/2015.
2. Tenenbein M. Do you really need that emergency drug screen? Clin Toxicol (Phila). 2009;47(4):286-291.
3. Saitman A, Park HD, Fitzgerald RL. False-positive interferences of common urine drug screen immunoassays: A review. J Anal Toxicol. 2014;38(7):387-396.
4. Nelson ZJ, Stellpflug SJ, Engebretsen KM. What can a urine drug screening immunoassay really tell us? J Pharm Pract. 2015.
5. Daniel J. Urine drug screens: Common false positives and negatives. S D Med. 2015;68(6):262-263.
6. Moeller KE, Lee KC, Kissack JC. Urine drug screening: Practical guide for clinicians. Mayo Clin Proc. 2008;83(1):66-76.
7. Breindahl T, Hindersson P. Methylphenidate is distinguished from amphetamine in drug-of-abuse testing. J Anal Toxicol. 2012;36(7):538-539.