At a Glance

Overdose from opioids can occur after ingestion of natural products, such as morphine and codeine, or after ingestion of semi-synthetic or synthetic opioids, such as heroin, oxycodone, hydrocodone, hydromorphone, fentanyl, methadone, or meperidine. Heroin is a commonly abused semi-synthetic opioid with no medical use. Although other opioids can be prescribed for therapeutic purposes, they are also frequently abused for their analgesic and euphoric properties. Opioid overdose may be fatal. Central nervous system (CNS) depression and respiratory depression are common and may be followed by Cheyne-Stokes respiration, cyanosis, and respiratory arrest. However, naloxone (Narcan) can reverse life-threatening opioid toxicity if administered promptly.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

A urine drug screen for opioids should be ordered in any patient presenting with a clinical history or symptoms suggestive of opioid overdose. Urine drug screens provide rapid turnaround and are available in most laboratories. Common urine drug screens available to detect opioid overdose include opiate, oxycodone, and methadone immunoassays. The opiate immunoassay is designed to detect morphine, but patients who ingest toxic levels of codeine, hydrocodone, and hydromorphone should have positive opiate screens. Heroin is rapidly metabolized to morphine, and heroin ingestion should also trigger a positive result on the opiate screen. Patients who overdose on oxycodone or methadone should have positive results on the oxycodone and methadone screen; respectively.

However, overdose from other semi-synthetic or synthetic opioids, such as fentanyl or meperidine, may not trigger a positive result on any of the commonly performed urine drug screening assays. If the clinical suspicion for opioid overdose is high, patients should be treated immediately with naloxone regardless of testing results.


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If available, confirmatory techniques, such as gas chromatography-mass spectrometry (GC/MS) or liquid chromatography-tandem mass spectrometry (LC-MS/MS), should be utilized to confirm the presence of a specific opioid and provide quantitative results if necessary.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

Urine drug screens have limitations, including the generation of false-positive and false-negative results. False-negative results may be seen if the opioid screening assay has low cross-reactivity for the ingested opioid. Unfortunately, oxycodone, oxymorphone, methadone, fentanyl, and meperidine have low cross-reactivity with most opiate immunoassays, and a urine drug screen may be negative after abuse of any of these drugs. For this reason, specific immunoassays are now commercially available for oxycodone and methadone. However, fentanyl, meperidine, and other synthetic opioids will not be detected by traditional urine drug screening panels.

False-positive results in the opiate assay can be seen in patients who consume poppy seed containing products or drink poppy tea, especially in opiate assays using the 300 ng/mL cut-off. Some laboratories have increased their cut-off to 2000 ng/mL to avoid false positives due to poppy seed ingestion. False-positive results on opiate assays can also occur in patients taking certain medications, such as levofloxacin.

Urine drug screens can be positive in patients taking therapeutic levels of opioids for pain management and results should be interpreted in the clinical context. Furthermore, urine drug screens are qualitative, based on a cutoff value, typically 300 ng/mL for opiates, oxycodone, and methadone. Negative results do not exclude the presence of opioids. Finally, urine drug screens can be positive for several days after opioid ingestion, and positive results may not indicate acute ingestion. Heroin is an exception.

What Lab Results Are Absolutely Confirmatory?

Confirmatory techniques, such as GC/MS or LC-MS/MS, can be utilized to confirm the presence of a specific opioid and provide quantitative results.

Heroin is rapidly metabolized to 6-monoacetylmorphine, the unique heroin metabolite. The presence of 6-monoacetylmorphine (6-AM) using a confirmatory technique confirms heroin abuse. However, because of the rapid conversion of 6-AM to morphine, 6-AM may be negative in patients who injected heroin more than 6-8 hours prior to testing.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

If urine drug screens and confirmations for opioids are negative, confirmatory analysis for fentanyl or other synthetic opioids not detected on routine screening or by traditional confirmatory techniques may be considered.