Laboratory support for emergency department drug testing

Christopher Holstege, MD, chief of the University of Virginia’s Division of Medical Toxicology, recalls a time when he and his colleagues didn’t routinely test for fentanyl use in patients who arrived at the emergency department (ED) with symptoms of drug use. “For the majority of my career at the University of Virginia, we didn't have fentanyl on the drug screen,” he said. “We just didn’t see it that much.”

That changed around 2013, when synthetic opioids, including fentanyl, began flooding the illegal drug supply. As the toxicology team at the University of Virginia started seeing greater fentanyl usage in the area, they worked with their laboratorian colleagues to incorporate a fentanyl test as part of their standard urine drug screening panels.

Updating drug testing panels to reflect local usage is an essential point of collaboration between EDs and the labs that run these tests. EDs often test for drugs of misuse — a less stigmatizing term for what were historically called “drugs of abuse” — in trauma patients, those who present with altered mental status, and special populations such as pediatrics. Emergency physicians observe the trends in and symptoms of drug use and know which tests their patients likely need, whereas laboratorians best understand which tests are available and how they work. Both play an instrumental role in ensuring patients get accurate and timely drug screen results.

The expertise of both sides, and their joint efforts, become all the more crucial as new drugs emerge. “We’re seeing such a plethora of drugs hit society,” Holstege said, adding that a lot of new opiates are hitting the market. At the same time, the emergence of new tests and testing methodologies for detecting these drugs makes EDs and labs better suited to respond but also gives them more options to weigh in any given drug use situation.

In response to this changing landscape, the Association for Diagnostics & Laboratory Medicine (ADLM) released an up-to-date guidance document (for which Holstege served as an advisor) that is designed to help both laboratorians and emergency physicians navigate testing for drugs of misuse.

New guidance for a new era

In 2003, the National Academy of Clinical Biochemistry — which is now called the Academy of Diagnostics & Laboratory Medicine — released a guidance document on ED drug testing. Twenty-three years later, an update was long overdue.

“It’s probably easier to say what hasn’t changed than what has [since 2003],” said Christine Snozek, PhD, co-director of clinical chemistry at Mayo Clinic in Phoenix, Arizona and co-author of the updated document. For starters, the new document recommends that EDs test for certain drugs and drug classes, such as fentanyl, oxycodone, and benzodiazepines, which were absent from the 2003 guidelines; conversely, use of propoxyphene and tricyclic antidepressants has declined, so testing for these drugs is no longer recommended.

Additionally, there have been improvements to the immunoassays emergency physicians often rely on for drug testing. For example, some laboratories now offer screens that can detect a broader range of benzodiazepines, Snozek noted. And mass spectrometry, which the guidance document recommends in cases where an immunoassay is insufficient and the result will inform the patient’s care, was not an option for many EDs in earlier decades.

“The ability to run a high-resolution mass spectrometry test on an ED sample in 2003 basically didn’t exist,” Snozek said.

The purpose of this testing, though, has remained constant: Instead of informing the emergency care a patient receives, identifying the drug or drugs they’ve been exposed to helps inform subsequent interventions.

“It’s not going to guide immediate management, because even if we get the results back in an hour, you’re not going to wait an hour to treat the patient,” said Stacy Melanson, MD, PhD, associate medical director of clinical chemistry at Brigham and Women’s Hospital in Boston, and guidance document co-author. The results can, however, “confirm your suspicion and help with more of a downstream management of the patient.”

For instance, a patient who arrives at the ER with signs of a drug overdose will immediately receive treatment, such as breathing assistance or naloxone, to manage their symptoms. Subsequently, a positive test on a urine drug screen could lead to a referral for behavioral medicine. Alternatively, a child with altered mental status testing positive for a drug of misuse could necessitate the involvement of Child Protective Services.

Urine drug screening also can obviate the need for more invasive and resource-heavy testing.

“I may not have to send a kid for a head MRI if I suddenly have a urine drug screen that comes back with marijuana [metabolites],” Holstege said.

Testing limitations and possible solutions

Compared with testing blood and saliva, urine offers the best combination of ease of collection, comparatively higher drug concentrations, and better availability of assays. However, urine can test positive for drugs after their effects have subsided, Snozek noted.

“A urine positive doesn’t necessarily correlate to the person’s behavior or symptomology at the moment,” she said. Thus, the document advises laboratories to educate EDs on the possibility that a positive result might indicate only past exposure, not a drug-related effect on current behavior.

Immunoassays are the most common method used for urine drug testing because of their rapid turnaround time and high-throughput compatibility, but the tests have several limitations. Cross-reactivity in broad-specificity drug class tests can cause false positives, while a test not sensitive enough or not designed to detect a particular substance can lead to false negatives.

In these situations, mass spectrometry-based tests can be instrumental in arriving at an accurate result but are themselves limited by the higher cost and complexity of running the assays, which can lead to a longer turnaround time. The document advises providers to consider if these factors will interfere with patient care, especially for those who might be discharged before results arrive.

Some EDs can order mass spectrometry tests from labs housed within their institution, which can mitigate those considerations. With that said, the guidance document is most relevant to hospital clinical laboratories that primarily use immunoassay tests and that might need to send samples to other labs for mass spectrometry testing.

“We tried to make the document as practical as possible, so it wasn’t really aimed at top tier reference laboratories with the best mass spectrometry technology,” Snozek said.

Mass spectrometry tests are used in cases where emergency physicians suspect drug use but immunoassays come up empty. It’s often through these more advanced tests that new trends in drug usage are identified.

“These tests may not change care, but we want to know exactly what the patient got into so that we have some idea of what's going on in the community,” Holstege said. This in turn informs those doing public health prevention work.

Education and collaboration

A large body of evidence suggests that providers may not be fully prepared to interpret drug test results. One study showed that most emergency providers report having received little to no training in the interpretation of drug tests, and another showed that most emergency physicians could not name the drugs tested for at their hospital.

“There’s a lot of confusion [among] the clinicians on the drug screens: What do they mean? What’s the utility of them?” Holstege said.

To address this, the guidance document advises clinical laboratories to provide EDs with relevant information on drug testing and interpretation. Labs can append comments to test results that note the possibility of false positives and negatives for a given immunoassay and direct emergency physicians to other educational materials that delve into why tests may be inaccurate.

As drug use patterns change and new tests become available, EDs and labs must engage in regular conversation about which tests they offer; the document recommends at least one such review per year.

“Clinicians really need to get to know their laboratory personnel,” Holstege said. The two often need to collaborate. In one recent example, Holstege had a patient presenting with all the typical signs of opioid exposure, including respiratory depression and response to naloxone, but the opioid panel came back negative. He communicated his strong suspicion of an opioid exposure to his laboratorian colleagues, who did further testing and obtained a positive result for nitazene, a synthetic opioid that’s been misused at growing rates in recent years.

EDs and labs should create protocols together for when to opt for mass spectrometry testing, including when to do so without a prior immunoassay. This requires the availability of affordable and accessible instruments and facilities, which in turn requires more federal funding.

“I would love to see the United States government put money into better detection methods at the hospitals,” Holstege said, especially in support of mass spectrometry testing in areas with great need.

“Emergency physicians rely heavily on laboratory results for a lot of their patients,” Snozek said. The ADLM guidance document aims to help EDs and laboratorians work together in support of their patients.

Yaakov Zinberg is a writer based in the Boston area. +LINKEDIN: www.linkedin.com/in/yaakov-zinberg-276056198