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URINE DRUG TESTING ELISABETH F. BILDEN, MD AUGUST 21, 2019

URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

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Page 1: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

URINE DRUG TESTING

ELISABETH F. BILDEN, MDAUGUST 21, 2019

Page 2: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

Case #1

• 6 y/o F BIBA to ED for generalized, persistent seizure activity• On arrival, seizure activity and wide complex tachycardia• Benzodiazepine + sodium bicarbonate boluses to treat seizure and anticipated acidosis• Endotracheal intubation• Wide-complex narrowed, mild tachycardia persisted, seizures stopped

• Urine drug screen not obtained in ED

• Admitted• No recurrent seizures or wide-complex cardiac rhythm

• PMHx- myoclonic epilepsy (ill-defined) over past 2 years

• Meds-felbamate, phenytoin, clonazepam, zonisamide

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Page 3: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

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Page 4: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens
Page 5: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

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Page 6: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

Case #1

• Extubated• Discharged• Recurrent episodes and readmissions• Urine drug test results available

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Page 7: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

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Page 8: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

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Page 9: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

Objectives

• List some indications for urine drug testing

• Discuss some general principles to apply when ordering and interpreting urine drug tests

• Describe potential benefits and pitfalls of urine drug tests

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Page 10: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

Indications and Settings for Urine Drug Testing

• Hospital (ED and inpatient)– Correlation to clinical presentation, i.e. exposure (maybe)– Information for inpatient setting (some requested for psychiatric admission)– Outpatient follow-up planning (chronic opioid treatment, MAT, public health)

• Outpatient (Primary care, pain clinic, MAT)

• Other – Clinical versus non-clinical settings– Substance Use Disorder additional treatment settings– Occupational – Child protection (abuse/neglect, pregnancy)– Specialty court, e.g. drug court– Public health– Post-mortem

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Page 11: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

Indications and Settings (MAT)

• Evaluate adherence to plan of care– Diversion, i.e. lack of detection of anticipated drug– Additional non-prescribed drug(s) present – Risk assessment, e.g. opioid + benzodiazepine – Public health/safety, e.g. unanticipated drug or other substance (adulterant, contaminant)

• Direct treatment – Follow-up intervals may be adjusted– Identify needs for additional resources/recommendations– Potential additional medication (non-MAT) changes

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Page 12: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

Commonly Used Methods for Urine Drug Testing

• Immunoassay (IA)– Identify drug classes – Based on similar drug structure and antibody recognition – Qualitative– Not confirmatory

• Chromatography– Separate/isolate analyte, e.g. gas chromatography (GC), liquid chromatography (LC)– Qualitative, although semi quantitative/relative to other substances detected and internal controls– Alone not confirmatory, part of the process for confirmation

• Mass Spectrometry (MS)– Identify and confirm presence of analyte by breaking apart– Quantitative report, qualitative or relative quantitative interpretation– Confirmatory

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Page 13: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

Immunoassays for Urine Drug Testing = “Urine Drug Screen” (UDS)

• Identifies drug (few) and drug classes (some)

• Positive test is based on similar drug structure and antibody recognition of the drug/site on drug

• Rapid turn-around-time (TAT)

• Qualitative

• Not confirmatory– May test for same drug classes but structures between classes may appear similar enough

to be detected (false positive)• e.g. Bupropion may trigger amphetamine

– May differ in detection of specific drugs and some drugs present in sample may not be detected on some tests (false negative)

• e.g. Clonazepam often not detected – Confirmation may identify presence (true positive) or absence (true negative) of drug

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Page 14: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

Case #2

• Prehospital– Adult male with history of SUD found unresponsive, respiratory rate 4-6, and sonorous

respirations– Good response, respiratory and neurological, to naloxone administration

• ED– Recurrent decreased level of consciousness– Low oxygen saturation, slow respiratory rate, and low blood pressure– Good response again to naloxone; no opioid withdrawal– Urine drug test negative for opiates, oxycodone, methadone, benzodiazepines,

barbiturates, marijuana, cocaine, amphetamines, and phencyclidine– Blood alcohol negative

• Hospital Course– Admitted to ICU– Recurrent opioid toxicity treated with naloxone– Discharge morning of hospital day # 3

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Page 15: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

Case #2

• History, clinical presentation, and assessment consistent with opioid toxicity (few other potential drugs)

• Urine drug test (IA) negative

• Patient reported chewing fentanyl patch

• Fentanyl (opioid) not detected on the hospital UDS used at that time = false negative

• No additional testing recommended

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Page 16: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

General Principles for Ordering and Interpreting Urine Drug Tests

• General– Get to know your lab resources: Individuals and testing capabilities– Variabilities exist in clinical approach between specialties and within specialty practices– Inform lab which drug(s) you are looking for

• e.g. buprenorphine– Testing and laboratory standards

• Valid and reliable• Clinical Laboratory Improvement Amendments (CLIA)

• Indications– Setting: MAT, specifically buprenorphine– Frequency/timing

• Start of new controlled substance• Every visit for Suboxone follow-up• Suspicion of misuse• Concern for diversion• Frequent early refill requests• Random testing if patient at high risk for misuse or physician recommendation

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Page 17: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

General Principles for Ordering Urine Drug Test

• Information obtained from test – Ensure patient taking/receiving intended medication(s)– Demonstrate exposure to unintended to drug/drug class, maybe– Exposure to substance consistent with presentation, not level of intoxication

• Information provided by test will be dependent on test type– Consider confirmation with GC/MS if unanticipated result or limitations make IA inadequate test

• Contributing factors– Availability of tests and lab personnel expertise– Tiered approach often used depending on indications and setting for test– Extent of testing/instrumentation available varies depending on location – “More than what’s in the manual”– Turn-around-time (TAT)

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Page 18: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

General Principles for Interpreting Urine Drug Tests

• Immunoassays– Laboratory test brand variability, e.g. not all benzodiazepine IAs/screens are the same– Specific test name to assist with determining which drugs might cause positive test

e.g. opiate versus opioid

• Presence of false positives and negatives – Confirmatory testing may be helpful in some instances

• Some factors affecting urine drug testing– Concentration of urine– Time, amount, and duration of drug/medication exposure– Pharmacology of drug: Formulation (IR versus ER), metabolic paths, elimination etc– Patient variabilities: Age, genetics, urine pH etc.

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Page 19: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

Detection Times - Sample

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Page 20: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

Procedures for Testing and Obtaining Urine Sample

• Ask patient what expect might find in urine

• Ask when last medication dose

• No belongings or other items in bathroom

• Colored toilet water

• Water source to in-bathroom sink off

• Observed if possible, more likely to be accurate/reliable

– Alternatives

• Confirm up to date care plan

• Specific plan for unanticiptated finding

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Page 21: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

Interpretation of Results

• Expected findings, continue plan

• Unexpected findings, confirm with chromatography/mass spectrometry– Negative test for medication patient should be taking– Positive unexpected results

• Determine/confirm they are not false positives• Positive THC if patient taking CBD

– Benzodiazepines special consideration given variability of IA test

• Plan in discussion with patient

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Page 22: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

Potential Benefits and Pitfalls of Urine Drug Testing: Benefits

• Identify and/or confirm exposure (maybe)

• Provide additional information for potentially adjusting plan of care if unintended finding

• Provide additional information for assessment and patient discussion, building trust

• Use advantages of urine specimen – Liquid state– Ease of sample collection– Non-invasive, sometimes– Drugs concentrated in urine– Longer window of detection than in blood– Captures results of drug metabolism

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Page 23: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

Potential Benefits and Pitfalls of Urine Drug Testing: Pitfalls

• Failure to recognize limitations of tests– Limited detection times– False positives

• Presumptive positive provides visual reminder to ask additional questions• Consider additional testing • Methamphetamine must have amphetamine on confirmation

– False negatives• Review some that are common (clonazepam, fentanyl)• Inform lab which is the drug of interest

• Treatment adjustments based primarily/only on test result

• Failure to recognize or lack ability to test for altered urine specimen – Altered pH due to additives such as ammonia or bleach– Altered specific gravity due to dilution– Lacking presence of metabolites (if confirmatory testing obtained)– Cooler temperature due to substituted urine

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Page 24: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

Drugs of Interest• Buprenorphine

• Common drugs of abuse– Opiates/opioids– Amphetamines/methamphetamines– Benzodiazepines– Cocaine– Marijuana

• Immunoassay availability– Barbiturates– Phencyclidine (PCP)– Tricyclic antidepressants (TCA/CA)

• Current drugs of abuse in the community (local, regional, state, national)– Newer psychoactive substances

• Synthetic cannabinoids• Synthetic cathinones• Synthetic benzodiazepines• Synthetic (analogues) fentanyls

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Page 25: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

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Opioids

Opiates

OpiumCodeineMorphineThebaine

Synthetics

Fentanyl(s)MethadoneMeperidineTramadol

TapentadolU-47700

Semi-synthetics

HeroinHydrocodone

HydromorphoneOxycodone

Buprenorphine

Page 26: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

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Page 27: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

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Page 28: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

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Page 29: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

Benzodiazepine Metabolism

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Page 30: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

Opioid Metabolism

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Page 31: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

Opioid Metabolism

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EDDP 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidineEMDP 2-ethyl-5-methyl-3,3-diphenylpyrrolidine

Page 32: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

Opioid Metabolism-Buprenorphine

• Cut-off 5 ng/mL versus 10 ng/mL

• Interpretation of ratios

– Buprenorphine

– Major metabolites• Norbuprenorphine• Buprenorphine-3-glucuronide• Norbuprenorpine-3-glucuronide

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Page 33: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

Opioids-Fentanyl Challenges

• Immunoassay testing – Limited parent compounds and metabolites, both pharmaceutical and analogues– False negative for some pharmaceuticals and some non-pharmaceuticals– Cross reactivity with trazodone and m-CPP (metabolite) and methamphetamine– Cost increase due to need for confirmatory testing

• Confirmatory testing – Limited parent compounds and metabolites, both pharmaceutical and analogues– False negatives for some pharmaceuticals and some non-pharmaceuticals

• One current test

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Page 34: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

Some Additional Confirmatory Testing Options

• “Comprehensive” OTC and prescription drugs

• “Compliance” Pharmaceuticals and non-pharmaceuticals

• “COAT” Limited number of substances and with confirmatory of the more commonly misused substances and soon to include gabapentin

• Isolated drug Specific drug and or metabolite

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Page 35: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

Discussion of Urine Drug Test Results with Patient

• Previously asked patient what might find in urine

• Ask patient for explanation– Positives

• Source of medication/drug that should not be present?– Negatives

• Why medication not in urine?

• Not punitive but finding may require action– Increase frequency of visits and/or testing– Warning– Taper, especially if diversion

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Page 36: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

Summary

• Why Indications for urine drug testing

• What Information wanted/needed

• Where Clinic setting

• Which Test(s) available

• How Obtain urine specimen

• When Frequency of testing

• Who Your lab personnel/experts

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Page 37: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

References

• Brown SM et al. Buprenorphine metabolites, buprenorphine-3-glucuronide and norbuprenorphine-3-glucuronide, are biologically active. Anesthes 2011.

• Dasgupta A. et al. Critical issues in alcohol and drugs of abuse testing (mult chpts/various auth). Elsevier 2019• Grunbaum AM et al. Laboratory principles in Goldrank’s Toxicologic Emergencies, 11th ed. Eds Nelson LS et al.

McGraw-Hill Education 2019.• Herrmann ES et al. Non-smoker exposure to secondhand cannabis smoke II: effect of room ventilation on the

physiological, subjective, and behavioral/cognitive effects. Drug and Alc Depend 2015.• Jannetto PJ et al. Executive summary: Amer assoc of clin chem lab medicine practice guideline-using clinical

laboratory tests to monitor drug therapy in pain patients. JALM, Jan 2018.• Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens.

Mayo Clin Proc 2017.• Moeller KE et al. Urine drug screening: practical guide for clinicians. Mayo Clin Proc 2008.• Paxton A. CBD flies off shelves, fosters uncertainty in tox lab. Cap Today May 2019.• Personal communications with lead laboratory personnel at DEA, Hennepin Tox, Essentia Health, and St. Luke’s.• Smith HS. Opioid metabolism. Mayo Clin Proc 2009.• Volkow N et al. Role of science in addressing the opioid crisis. NEJM 2017. • Wu A et al. National academy of clinical biochemistry laboratory medicine practice guidelines: recommendations for

the use of laboratory tests to support poisoned patients who present to the emergency department. Clin Chem 2003.

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Page 38: URINE DRUG TESTING - CHI St. Gabriel's Health · 2019-11-21 · • Moeller KE et al. Clincal interpretation of urine drug tests: what clinicans need to know about urine drug screens

Thank you

The End