Urine Drug Screen

The urine drug screen is a rapid immunoassay that detects drugs or their metabolites in urine over a set cut off concentration, using antibodies that react with a class of compounds. Confirmatory testing with gas chromatography or liquid chromatography coupled to mass spectrometry identifies and quantifies the specific substance and is the only reliable way to prove a result. Urine is the preferred sample because drugs are concentrated and detectable for days.

The test is used in emergency medicine for the undifferentiated poisoned or comatose patient, in addiction and pain services to monitor adherence and abstinence, in occupational and forensic settings, in antenatal and paediatric care when exposure is suspected, and before transplant or surgery in selected patients. It confirms exposure, not impairment, intoxication or the time of use.

Drug use is common: about 296 million people used illicit drugs worldwide in 2021, and cannabis is the most used. Opioid overdose causes more than 100 000 deaths a year in the United States alone, and synthetic opioids such as fentanyl are often missed by routine screens. Acute poisoning accounts for about 1 to 2% of emergency presentations.

Indications. Altered consciousness of unknown cause, suspected overdose or toxic ingestion, unexplained seizures, agitation, psychosis or chest pain in a young person, monitoring of patients on opioid substitution or controlled drugs, child protection concerns, pregnancy with suspected drug use, and occupational or legal requirements.

Specimen. A fresh random urine sample, 30 to 60 mL, collected under direct observation or with checks against tampering when the result has legal or treatment consequences. The laboratory checks temperature (32 to 38 °C within 4 minutes), creatinine (under 2 mmol/L, or under 20 mg/dL, suggests dilution), specific gravity, pH and oxidant adulterants. Samples are stored at 2 to 8 °C for up to 7 days and frozen for longer.

Typical immunoassay classes, cut offs and detection windows. Cut offs vary by assay, and the numbers are typical screening values.

Interpretation.

• A positive screen is presumptive. Confirmation by mass spectrometry is needed before any action with legal, employment or child protection consequences.
• A negative screen does not exclude exposure, because of timing, cut offs, and drugs not in the panel (novel psychoactive substances, synthetic cannabinoids, gamma hydroxybutyrate, ketamine, tramadol, zolpidem and many fentanyl analogues).
• Metabolite ratios and the presence of the parent drug help to separate recent use from past use.
• A very dilute sample (creatinine under 2 mmol/L) with a negative result is not reliable and is repeated.
• Quantitative changes cannot be used to judge dose or time of last use.

Common false positives.

• Amphetamines: pseudoephedrine, phenylephrine, bupropion, labetalol, ranitidine, trazodone, selegiline.
• Opiates: poppy seeds, codeine containing cough syrup, rifampicin on some assays, quinolone antibiotics.
• Benzodiazepines: sertraline, oxaprozin.
• Cannabinoids: efavirenz, pantoprazole on some assays, and non-steroidal anti-inflammatory drugs on older assays.
• Phencyclidine: dextromethorphan, ketamine, venlafaxine, tramadol.
• Tricyclic antidepressant screen: cyclobenzaprine, carbamazepine, quetiapine.

Critical values and findings needing immediate action.

• A positive result in an unconscious patient or one with respiratory depression: do not delay naloxone and airway support for a result, because the test is not required for emergency treatment.
• Positive opioids or benzodiazepines with respiratory depression and hypotension.
• Positive cocaine or amphetamine with hyperthermia, hypertension, chest pain, seizures or agitation.
• Positive result in a child or a pregnant woman: safeguarding and obstetric or paediatric review.
• Negative screen in a patient with a clinical toxidrome: send blood for specific drugs (paracetamol, salicylate, ethanol) and a broader mass spectrometry panel.

Interferences and pitfalls.

• Adulteration (bleach, nitrite, glutaraldehyde, pyridinium chlorochromate, soap, vinegar), substitution and dilution defeat immunoassays. Observed collection and validity testing limit this.
• Immunoassay panels miss many synthetic opioids, synthetic cannabinoids and designer drugs.
• The test does not tell the dose, time or route of use, and detection window varies with dose, frequency, metabolism, kidney function and urine pH.
• Passive exposure to cannabis smoke rarely gives a positive screen.
• Cut off choice changes sensitivity, and a low cut off increases false positives.
• A positive urine for cannabis does not mean the patient is impaired.
• Hospital drugs given (midazolam, fentanyl, morphine, ketamine) cause positive results.
• Benzodiazepine screens are poorly sensitive, and a negative screen in a patient on lorazepam is common.
• Results must be interpreted by someone aware of the prescribed medicines.

Special groups.

• Children: unintentional ingestion (opioids, tricyclics, clonidine, sulfonylureas), and the screen is limited.
• Pregnancy and neonates: maternal drug use is detected in neonatal urine, meconium or cord tissue, with meconium having a longer window.
• Adolescents: synthetic cannabinoids and designer drugs are missed.
• Patients on chronic opioid treatment: ordinary treatment gives positive tests, and mass spectrometry confirms the specific drug.
• Regions: availability of confirmatory testing is limited in many settings, and local drug patterns (khat, tramadol, kratom) are missed by routine panels.

Follow up tests. Confirmatory mass spectrometry, serum paracetamol and salicylate, serum ethanol and osmolal gap, blood gas, ECG for QRS and QT intervals, creatine kinase, troponin, creatinine, glucose, liver function tests, specific drug levels, and a repeat urine in 24 to 48 hours when the history and result do not match.